Neuroscience Lecture: Resting Potential

all right everybody so in this lecture up to this point now we we&#39;ve kind of discussed the gross anatomy of neurons uh we&#39;ve discussed other cells in the brain glial cells uh and just basically how it is that they differ physically in in terms of their their size their shape and their parts from the other types of cells that we find throughout the body in this lecture we&#39;re going to start to get into the ionic basis of what it is that makes them excitable cells and there&#39;s two components of that the first of which is the resting potential the neurons spend the majority of their time at rest and the second of which is the action potential which we&#39;ll cover later before we jump into that I do want to mention really quickly if you&#39;re looking on the canvas under the modules section after certain lectures you can see I&#39;ve got the PDFs of the slides there for you to study without having to go back and listen to the whole lecture again but in addition to that occasionally you will see practice games using Materia and there there are some practice games for the resting potential the action potential Etc you are not required to complete these but they do um students do find them useful in terms of helping to study and helping to to practice these Concepts so I encourage you to check those out uh let&#39;s begin then so our goals for today uh uh is to discuss what it means for a neuron to be at rest what contributes to that and we&#39;ll find that that has to do with some unique proteins at the level of the phospholipid bilayer the membrane uh we&#39;ll talk about ionic concentrations and we&#39;ll talk about channels um and uh and how that they how they affect these things and and contribute to the state in which the neuron is not communicating with other neurons so let&#39;s begin here uh the study of some of these processes that we&#39;re going to talk about really could be grouped within as I mentioned I think in the first lecture there&#39;s there&#39;s many subfields of Neuroscience and uh this particular sub-discipline or or sub area of study would be referred to as neurophysiology so we&#39;re looking at how it is that the processes within cells both electrical and chemical uh their makeup their physical makeup Etc uh govern their ability to Signal okay so as I say we&#39;re talking about the resting potential today the opposite component to that is the action potential the action potential is when the neuron actually rapidly sends an electrical signal an electrical signal travels down its axon and then it sends a message typically a chemical message across the synapse to another neuron as I said though the majority of a neuron&#39;s lifespan is spent at rest technically uh so action potentials are very brief blips in changes in the membrane potential don&#39;t worry we&#39;ll explain what a membrane potential is but again the majority of the time it is at rest uh We&#39;ve covered what neurotransmitters are in the previous lecture we&#39;ve covered what synapses are um and so now we&#39;ll see just essentially again what is the neuron doing when it&#39;s not signaling so to introduce this concept I want to kind of drive home the uh the importance of what it is that we&#39;re talking about here and that has to do with electricity what makes neurons special is that they have this ability to store and release electrical charge in the form of different different manners right but in a sense they are little batteries right that&#39;s that&#39;s what uh that&#39;s what that&#39;s what it means to store and release electrical charge this is a very special process so I want to just get us prepared for that aesthetically uh with a with a clip from one of the greatest films of all time here battery and over 25 000 and 18 years combined with a form of fusion the machines had found all the energy they would ever need a field endless feelings for human beings are no longer born [Music] for the longest time I wouldn&#39;t believe it and then I saw the fields watch them liquefy the dead so they could be fed intravenously to be standing there facing the pure horrified precision I came to realize the obviousness of the truth what is the Matrix control The Matrix is a computer-generated Dreamer built to keep us under control in order to change the human being into this no I okay so we&#39;re thinking about batteries here we&#39;re going to be thinking about electricity quite a bit uh as we move forward and again the metaphor I think will hold that neurons themselves are very much like batteries we&#39;re going to break down the different components of electricity that govern these properties here in a little bit but first let&#39;s talk about our cast of chemicals that are involved and beginning at the level of ions Okay so when the neuron is at rest the resting potential itself is reflecting this balance between various electrochemical forces particularly diffusion and electrostatic pressure these are the result of ionic concentrations so we all know that cells have an intracellular fluid which is separate from the extracellular fluid the outside area and it&#39;s separated by this lipid membrane we&#39;re going to talk about that in a little bit we&#39;ll expand on that but in particular what makes this special is that the fluid on the inside of the cell and on the outside of the cell differs slightly in terms of the ions or at least the amount of ions that are within it particularly the distribution of what are called anions and cations anions are negatively charged cations are positively charged okay so there are four of which that are the most common that we&#39;re going to talk about throughout this semester and those would be sodium potassium chloride and calcium so note all but one of those is a cation is positively charged uh chloride is an anion it is negatively charged we&#39;ll talk about that when we talk about gaborergic neurons later but the distribution of these anions and cations uh between the two spaces the difference in that distribution is what contributes to electrical charge or electrical potential the difference in charges and don&#39;t worry if you&#39;ve never taken you know a physics class where they&#39;ve broken down this kind of stuff we&#39;re going to get through it we&#39;re not going to get lost in the weeds our goal here is to understand the the electrical component of this enough that it serves us to understand how to work with the cells um so as I mentioned ions are dissolved throughout fluid in the body okay there are ions in the extracellular fluid and there are ions in the intracellular fluid and they&#39;re separated by the membrane of the cell now one of the things that we&#39;re going to find that&#39;s special about neurons is that they have unique a unique cast of proteins throughout their membrane which form like Gates which can open and close and allow in and out the flow of certain ions and that ultimately is what allows the neuron to transition from one level of voltage or potential to another the resting potential to the action potential so let&#39;s review our phospholipid membrane everybody here in this class has had your biology prerequet at this point and certainly I think um this is probably review and that you you understand what the phospholipid membrane is but let&#39;s go through it really quickly and then we&#39;ll learn how neurons can break some of the rules here so uh this in particular the phospholipid membrane right we&#39;re dealing with aspects of molecules that are hydrophilic which means they um they do not repel water okay they&#39;re water loving quote unquote they dissolve in water and so our ions are hydrophilic they dissolve in water um and then we have our hydrophobic compounds which are water fearing they do not dissolve in water they repel water and again at the level of the chemistry this is due to differences in electrical charge we&#39;re not super worried about that here you can think more about that in a chemistry class uh but let&#39;s just state that lipids right fatty lipids are hydrophobic okay this is why if you put olive oil in water it floats right the little the you&#39;ll see the beads of the olive oil floating and through the water because the olive oil is a lipid it is hydrophobic okay so the membrane of neurons and indeed all cells is composed of these long nonpolar chains of carbon binded to hydrogen bonded to hydrogen which we refer to as phospholipids and the phospholipid bilayer itself is arranged in such a way that you have these polar heads okay uh facing outward toward the extracellular fluid and toward the intracellular fluid which are hydrophobic and the tails are arranged forming the inner component of the layer uh facing toward each other which are nonpolar okay and hydrophilic so this is the extent of which you need to know there again we&#39;re not super concerned with the biochemistry in this but just the takeaway is that we have a membrane which is keeping the extracellular fluid out from the intracellular fluid and we&#39;re going to find that the membrane has special proteins that act like gates in it which can briefly allow this to change so what are these special proteins okay well they are some of them are called ion channels in fact today with what we&#39;re talking about in regards to the resting potential ion channels are the most important component for maintaining the resting potential so these are proteins which span the membrane let me get my laser pointer out here we can see our phospholipid membrane and here we have this protein which is composed of you know different polypeptide subunits okay and part of the this this protein is is facing outside of the membrane part of it is inside the membrane so we say it is membrane spanning okay so here it is and this is an ion Channel it is a special type of protein which can open up and allow the flow of certain ions from outside of the cell into the cell and in some cases it can allow the flow of certain ions from inside of the cell to go outside of the cell so they are specialized these proteins in the way that they&#39;re made up their charges Etc are specific in such a way that they only allow certain ions to flow through them so there are different types of of ion channels um and in response to how it is that they open or close they require different types of stimuli so we call these gated ion channels and they can open or close in response to changes in voltage that would be called a voltage-gated ION channel and so that would open or close if the voltage of the neuron rises above a certain point or dips below a certain point that will automatically open or close a voltage-gated ION channel um there are chemically gated ion channels which we call ligand gated ion channels a ligand in biology is just a molecule which binds with a substrate okay it&#39;s like a key that fits into the lock in a door okay neurotransmitters are ligands all right so sum gated ion channels are opened by chemicals by neurotransmitters like a key going into a lock and opening the door some of them are open and closed in response to Mechanical action so we&#39;ll see that there are ATP powered pumps like the sodium potassium pump and this opens and closes mechanically and is powered by ATP and it allows sodium and potassium to flow through it there are other types of membrane spanning proteins forming channels okay that we&#39;re going to talk about later in this course uh things like G protein coupled receptors okay they&#39;re a little bit more complex in the way that they work so we&#39;re going to focus on those later when we talk about neurotransmitter systems but for today we&#39;re really going to focus on voltage-gated ION channels and the sodium potassium pump so ah let&#39;s talk about the ionic concentrations of a typical neuron inside the cell versus outside of the cell so the Hallmark of the neuron at rests is that it contains this large amount of negatively charged proteins take a look here negatively charged proteins inside of the neuron okay so these are the things inside the cell you know making up stuff like I don&#39;t know the endoplasmic reticulum uh Golgi apparatus all that kind of stuff that you already are familiar with right these are overwhelmingly negatively charged and they&#39;re large so this means first off you&#39;ve got a net negative charge inside the neuron generally due to all these large negatively charged proteins comparatively outside the cell the extracellular space extracellular fluid there are very few negatively charged proteins okay so that&#39;s our first difference extracellular fluid tends to be more positively charged than the interior fluid of a neuron and one of the big reasons for that is because the interior of the neuron has all these large negatively charged proteins in it but what about ionic concentrations well here we see some differences as well outside the neuron in the extracellular fluid there&#39;s a whole lot of positively charged sodium ions and there is a small small number of positively charged potassium ions inside the neuron there is a very small amount of positively charged sodium ions and a relatively large amount of positively charged potassium ions however that is not enough to overcome the net negative charge of all the negative proteins inside there so we&#39;ll come to find that when the neuron is at rest it has a net negative charge typically around negative 65 millivolts okay and for the neuron to send a chemical message when it leaves the resting potential it&#39;s moving away from negative 65 and eventually up into the positive in order to do that what&#39;s going to happen is that we need to shift the balance of these ionic concentrations generally we need to bring more sodium into the cell to help raise that potential up in the positive direction there don&#39;t worry about that just yet but just kind of be thinking about the distribution of charges let&#39;s break down electricity really quickly the major components that we&#39;re concerned about here all right and again we have our our analogy of the battery okay and uh a battery is something through which current can flow current is the movement of electrical charges it&#39;s measured in amps so electrical current is really just reflected electrical charge movement of electrical charge is just reflecting in any case in a battery whatever movement of ions okay because ions are positively or negatively charged their movement that is movement of electrical charge okay electrical potential that that&#39;s the term that we use in Neuroscience frequently is we&#39;ll refer to a membrane potential and action potential a resting potential we use potential synonymous with voltage okay voltage is the force which is being exerted on a given particle at a given time and it&#39;s measured in volts okay it&#39;s due to the difference between the anode and cathode regions which are positively charged regions and negatively charged reasons regions okay so if you had a battery okay with an ant with an anode and a cathode end that&#39;s suggesting that on the one end of the battery there are more positively charged ions and on the other end there are more negatively charged ions and the difference between these two the larger the difference between them creates a larger potential a potential for like energy you can even think about really and that potential is the voltage the larger the potential the more Force there is to move those ions if necessary Opposites Attract remember that okay you got a lot of positive charge one way and a lot of negative charge one way what happens okay well they want to come together there&#39;s a lot of energy trying to push them together strong magnets are like this right trying to pull them together rather that&#39;s almost analogous to what we&#39;re talking about here let&#39;s talk about conductance conductance conductance is the relative ability of an electrical charge to move from one point to another it&#39;s measured in Siemens okay and conductance is the inverse of resistance resistance the relative inability of an electrical charge to move from one area to the other this is measured in ohms so we&#39;ll find particularly that resistance and conductance are important when we consider axons later when we&#39;re talking about the action potential how is electricity kept inside the wire right how does it flow how does it move there&#39;s a certain amount of resistance that&#39;s involved right keeping it flowing along almost like a tube of toothpaste being squeezed through there down the wire we&#39;ll get into all that later all of these components come together to form something called Ohm&#39;s law Ohm&#39;s law Ohm&#39;s law states that current I is equal to conductance multiplied by voltage that&#39;s what gives you current okay now we don&#39;t want to get too lost in these but for the exam you should know you should be able to Define potential and voltage what is that well it&#39;s the force exerted on a particle she able to Define conductance it&#39;s the ability of a particle to move Define resistance it&#39;s the inability of a particle to move to find current all of these they might sound like a bunch of of the gobbledygook right now but when we start to talk about changes in the potential of the neuron you&#39;re going to start thinking about these in your head and they&#39;re going to come together and they&#39;re going to make sense I promise all right back to the resting potential I kind of already gave this away on the last slide we said that when a neuron is at rest when it&#39;s inactive it&#39;s not doing anything it&#39;s typically sitting at about negative 65 millivolts Okay negative 65 millivolts that number that potential is a reflection of the difference in charge on of the ionic concentrations on the inside of the neuron versus the outside of the neuron how do we know this well if you were to use a a reference electrode and you were to place on a reference electrode uh let&#39;s say onto the axon of a neuron okay you place it inside there so that it&#39;s sampling the electricity in the intracellular fluid you then take another electrode and you place it outside of the neuron and you measure the uh electricity in that fluid the the potential in that fluid okay the difference between those numbers is what shows up as our potential and that&#39;s negative 65 when the neuron is at rest so a lot of negatively charged proteins inside the neuron at rest a little bit of sodium a lot of potassium outside the neuron lots of positively charged sodium a little bit of positively charged potassium no or very few negatively charged proteins and so you have a situation where one number the outside is going to be higher than the inside number which creates a difference and it kind usually winds up being around negative 65 now um we say that this is an average at rest okay in reality that number will fluctuate based on events things like the movement of the sodium potassium pump Etc typically in an average neuron it&#39;ll fluctuate between negative 50 to negative 80 millivolts and so we say the average resting potential is negative 65. this is in the beginning of the course um we try to stick with an average number but we&#39;ll find later on in this course that some neurons break this Rule and have a different average resting potential and they tend to be specialized neurons in areas of like sensory systems so involved in like the ear or the eye but overwhelmingly in terms of neurons in the brain we&#39;re seeing this negative 65 average okay and that that resting potential that average is a reflection of fluctuations moving between negative 50 to negative 80 millivolts so here we have our membrane and we&#39;ve talked about at this point that there are certain membrane spanning proteins which we call ion channels and they are permeable to specific types of ions some of them are permeable to potassium some are permeable to sodium and we&#39;ll find throughout this course there&#39;s a great deal of variability uh in terms of what it is that they&#39;re permeable to today the most important ones we&#39;ll talk about are sodium and potassium channels now when the neuron is sitting at rest the majority of these ion channels in the membrane are closed the majority are closed okay this makes sense uh the neuron sitting there it&#39;s not doing much and so the gates are closed it&#39;s at rest it&#39;s not taking any visitors today the gates are closed right if the gates were to open that would cause a change in flow of ions and likely cause them the neuron to move away from the resting potential so most of the gates are closed there is however a small small small proportion of potassium channels that are special potassium channels that are always open they never close they&#39;re always open these are called leak potassium channels leak potassium channels so they are leaky they are constantly allowing potassium to flow in and out of the cell okay in small amounts that&#39;ll be important later when we talk about the sodium potassium pump remember that there is a lot of potassium ions inside the cell at rest and relatively few outside the cell we&#39;ll come back to this here shortly foreign so I mentioned this earlier right the neuron at rest the resting potential that difference in potential charges is reflecting a balance between two different forces one of which is diffusion and the other witches of which is electrostatic pressure let&#39;s talk about diffusion diffusion is the idea that uh ions want to diffuse or flow down their concentration gradient okay what does that mean well let&#39;s look at this image on the bottom left here if you take a cup of water and you drop food coloring a single drop of food coloring into the water what happens okay the single drop of food coloring is highly highly concentrated it contains many many many molecules of this particular coloring which are concentrated in a small tight space when it hits the water it spreads out it diffuses those molecules spread throughout the medium of the water they move from an area of high concentration to an area of low concentration they spread out they diffuse okay uh another way to think about this is like being in a crowded elevator you walk into the elevator there&#39;s a bunch of people already in there boy you don&#39;t want to be in there it&#39;s claustrophobic you can&#39;t wait to just get out you want to diffuse down your concentration gradient out into the Hall where there&#39;s people are more spread out and you don&#39;t feel so crammed together that&#39;s diffusion okay and we see another example of that in this figure here okay tight concentration of these little beads in this cup you pour it into a bigger area like the hallway I was mentioning and they spread out okay they spread out across their concentration gradient so uh diffusion is the idea that ions want to move from areas in which they are crowded which there are many of them concentrated to areas where they are less concentrated so uh let&#39;s take a look at how diffusion works with these uh membrane channels okay or semi-permeable member the semi-permeable membrane we call it the membrane semi-permeable right because it has channels in it that can open and close right and so sometimes it&#39;s permeable sometimes it&#39;s not right so membrane permeability it changes right depending on what&#39;s going on with the neuron depending on how many gates are opened or closed depending on what kind of gates are opened or closed whether they&#39;re potassium Gates sodium Gates whatever right that alters the membrane permeability okay so here in this image in the bottom portion you can see that let&#39;s take a look here we have a few a couple different types of channels let&#39;s imagine we&#39;ve got a semi-permeable membrane separating uh the fluid in this cup we&#39;ll call it separating the fluid on the left from the fluid on the right and there&#39;s two different types of beads in here we&#39;ve got these blue beads and these red beads okay red beads are larger than the blue sure uh we&#39;ve got three channels in the membrane two of these channels are selectively permeable to blue beads to blue beads and so blue beads are free to flow across the membrane and diffuse uh along their concentration gradient and you can see that here there&#39;s an even concentration of blue beads on the left and the right side because they&#39;ve been flowing through those channels if there was more blue beads on the left they would flow through until it was evenly dispersed with the left and the right note that this channel on the middle though is closed and it is impermeable to the red beads we&#39;ll say it&#39;s closed it&#39;s impermeable to the red beads in this state so the red beads stay on the left side they can&#39;t move they might want to move and diffuse but they can&#39;t because the channel the gate doesn&#39;t allow them through and so here in this instance in this example we might imagine that the channels which are open and allowing those blue beads through are are our leak potassium channels that are remaining open that are allowing them to flow in this case now you may be thinking well hey wait a minute uh if there&#39;s a lot of potassium inside the cell and a little bit outside the cell why doesn&#39;t the potassium flow completely down its concentration gradient so that there&#39;s an equal amount of potassium inside and outside we&#39;re going to talk about why that is here shortly if you&#39;re thinking along those lines though good job that&#39;s uh that&#39;s thinking and paying attention to the details and I promise it&#39;ll make sense here shortly before we get to that though let&#39;s talk about our second force that matters electrostatic pressure okay electrostatic pressure this is that simple concept that you all learned in grade school when you were learning to play with magnets okay you learned that Opposites Attract and likes repel that is electrostatic pressure it&#39;s due to the distribution of charges if you have a lot of positive charge on one side and a lot of positive charge on the other and you try to bring them together they&#39;re going to be forced apart they&#39;re going to want to go away from each other if you have a lot of positive charge on one side a lot of negative charge on the other they&#39;re going to want to come together and if you resist that coming together with your hands say you&#39;ve got two strong magnets and you&#39;re physically holding them so that they&#39;re apart they want to come together but you&#39;re holding them apart it takes a certain amount of force resistance on your part to do that that&#39;s analogous to again a potential right the amount of voltage there right the stronger it is the stronger the difference in charge between those two the stronger the potential the stronger the voltage the harder it is for you to resist and keep those magnets apart okay so our third key player here that is involved in maintaining the balance between electrostatic pressure diffusion it&#39;s maintaining a balance of charges a balance of flow of ions is the sodium potassium pump okay it pushes sodium out of the cell and it brings potassium into the cell this is that key point where if those of you in the previous slide were thinking hey if the leaked potassium channels are always open why doesn&#39;t all the potassium just flow right on out of the cell until it&#39;s equivalent with the potassium on the outside well here&#39;s your answer okay the answer is that potassium is Flowing out of the leak potassium channels a little bit at a time because there&#39;s not a lot of them but it is Flowing out a little bit at a time constantly but the actions of the sodium potassium pump are constantly bringing some potassium back into the cell so some potassium is leaving and at the same time some potassium is being brought back in this maintains that difference where you&#39;ve got more potassium inside relative to the outside take a closer look at that here&#39;s our sodium potassium pump and what it&#39;s doing specifically it&#39;s always operating at a consistent rate it&#39;s powered by ATP and what it&#39;s doing is it pumps two potassium ions into the cell for every three sodium ions that it kicks out of the cell now what does that mean it means that the actions of the sodium potassium pump are going to help to yield and maintain that net negative charge inside the cell it&#39;s bringing less positivity in for the amount of positivity it&#39;s kicking out it kicks three positive sodium ions out for every two potassium positive ions it brings in meanwhile leak potassium channels are open and some amount of potassium is always trying to leave down its concentration gradient this constant movement reflects a balance and it builds up a fluid equilibrium which is close to the equilibrium potential for potassium that means that the amount of potassium flowing out is equivalent to the amount being brought in at any given point in time the resting potential is usually very close to the equilibrium potential for potassium we&#39;ll talk more about that in a little bit let&#39;s talk about though why it is or how it is that the neuron fluctuates between about negative 50 to negative 80 millivolts okay it moves like like a needle on a dial kind of back and forth it&#39;ll go down all the way maybe to negative 80 and then it&#39;ll go up up up up up up up up closer to negative 50 and then it&#39;ll go back down down down down down why is that happening well let&#39;s think about this in conjunction with the leak potassium channels and the sodium potassium pump all right you get a lot of large negatively charged proteins inside the cell okay here they are in Gray all right cells got a net negative charge you&#39;ve got a lot of potassium inside the cell all right the sodium potassium pump is bringing more potassium in and as potassium keeps building up building up building up building up inside the cell what&#39;s going to happen well as it gets to be more and more crowded inside the cell there&#39;s more and more potassium and those leak potassium channels are staying open what&#39;s going to happen diffusion is going to cause more and more of those potassium ions to leave so this is how you get that fluctuation between negative 50 to negative 80. okay at negative 50 there&#39;s probably more potassium ions inside the cell uh and then what happens is they begin to diffuse out more rapidly out out out out and you see the the cell go from negative 50 down to negative 60 to negative 65 to 70 to 80. well now there&#39;s not as much potassium anymore so diffusion has slowed down there&#39;s not much potassium leaving because because there&#39;s not much in the in the cell so it doesn&#39;t want to diffuse right it&#39;s not as crowded anymore well the sodium potassium pump this whole time is bringing more potassium in eventually it&#39;ll begin to build back up build back up build back up and then it&#39;ll begin to diffuse out more rapidly all right so that&#39;s how the leak potassium channels in conjunction with the sodium potassium pump create this ebb and flow between neg 50 to neg 80 and this is how we wind up with our average resting membrane potential around negative 65 millivolts we&#39;re sitting at rest here in the coming lectures we&#39;ll find that when we move past negative 50 something special occurs keep in mind too we&#39;re always kicking out three sodium ions at rest again making sure that there&#39;s very little sodium inside the cell helping to maintain a net negative charge so this slide is reviewing everything that I just said here right so as the cell becomes more positive it becomes more crowded the potassium sodium potassium pump has brought more potassium in potassium will begin to diffuse out the leak potassium channels down its concentration gradient okay but what about after a bunch of potassium has diffused out maybe the cells down to about negative 80 millivolts now now what&#39;s going to happen well now our second force is going to act electrostatic pressure the cell has become more and more negative inside and you&#39;ve got a lot of positivity outside the cell well the more negative the cell is the more that positivity wants to get in right Opposites Attract electrostatic pressure and well how is that positivity going to get back in the cell some of it&#39;s coming in through the sodium potassium pump but very little a little at a time slowly okay what&#39;s the other thing the way that this could occur let&#39;s imagine that we&#39;re not talking about any other Gates being open we&#39;ve just got our leak potassium channels open okay well guess what uh if it&#39;s really negatively charged inside uh then that pull Opposites Attract those positively charged potassium ions are going to want to come back in right because they&#39;re attracted to that an area of negativity okay so electrostatic pressure will bring potassium ions back in through the leak potassium channels eventually they&#39;ll build up build up due to the actions of electrostatic pressure but also the sodium potassium pump and then they&#39;ll diffuse back on out again it&#39;s a constant ebb and flow back and forth yeah all right so again this ebb and flow this balance between the force of diffusion and electrostatic pressure and if you guys are taking notes Here an easy way to remember this diffusion is typically talking about ions diffusing and leaving the cell okay leaving down their concentration gradient moving from a crowded area because the intracellular space that&#39;s like the elevator right it&#39;s small it&#39;s crowded to a large less crowded area the extracellular space diffusion leaving the inside of the cell going to the outside electrostatic pressure though is about things being brought in from the outside to the inside right keep that in mind it&#39;s an easy way to remember the difference between those two let&#39;s talk about the equilibrium potential really quickly here I mentioned this earlier we said that at rest the neuron uh its membrane its resting membrane potential is typically quite close to what we refer to as the equilibrium potential for potassium what is the equilibrium potential it is the point at which the flow of a given ion is equivalent in both directions meaning that you have a balance between the amount of the ion that is leaving and the amount of the ion that is being brought in okay the equilibrium potential for potassium would mean that there is an equivalent amount of potassium in terms of charge leaving as is entering right in reality the resting membrane potential is going to fluctuate up and down as we said and it&#39;s going to move closer to the equilibrium potential for potassium and then move away from it that&#39;s usually what&#39;s happening okay now the equilibrium potential can be calculated for all sorts of different ions okay not just potassium but sodium other things too right uh you can use an equation to calculate this called the nernst equation now the nernst equation I&#39;m not going to ask you guys to derive that I don&#39;t think it&#39;s useful for you in this course but just know that what it&#39;s taking into account is um the potential um that would be needed in terms of balancing the force the voltage to push a single ion across the membrane at a given time relative to those leaving okay so it&#39;s going to take into account things like resistance of the membrane which is going to be governed by the amount of channels that are opened or closed okay it&#39;s taking into account conductance all those sorts of factors and so the nernst equation can calculate the equilibrium potential for a single ion there are other equations in neurophysiology used as well which can calculate the equilibrium potential of permeability for multiple types of ions and this is more accurate to reality because in reality the membrane is permeable to more than just one ion okay it&#39;s permeable to more than just potassium it also has areas that are permeable to sodium or or maybe calcium or any other number of ions in order to calculate all of these permeabilities at once to to come up with an equilibrium potential you use something called the Goldman equation again I&#39;m not going to make you all derive that but just understand that it&#39;s a reflection of the resistance of the membrane how many gates are opened versus how many are closed uh these sorts of things okay so for my purposes for the exam it&#39;s enough for you to just know what the nernst equation is what the Goldman equation is what the equilibrium potential is how the equilibrium potential is related to the resting potential and particularly how&#39;s it related to the action or to the flow of potassium how does that relate to leak potassium channels and how does it relate to the sodium potassium pump I have here I&#39;m not gonna go through this video uh in the in the lecture since this is recorded but I have posted this video in the uh modules section underneath this lecture okay it&#39;s a summary video of everything we&#39;ve just talked about so when you get done watching this video watch this uh little summary it&#39;s a short uh few minute summary of everything I just talked about and it puts all the pieces together uh in to form the resting membrane potential so check that out after this lecture is over okay let&#39;s delve a little bit deeper into uh channels particularly potassium channels why potassium channels because they&#39;re super important and I think I&#39;ve emphasized that at this point that you know potassium channels there&#39;s different types of potassium channels there are voltage-gated potassium channels there are ligand-gated potassium channels but we talked about a special type of potassium Channel today called the leak potassium Channel all neurons have leak potassium channels which are always open now depending on the type of neuron what it&#39;s specialized for it may have more or less leak potassium channels than another uh but all neurons have these okay so potassium channels in terms of gated ion channels or types of ion channels they&#39;re one of the really important ones if you mess with potassium channels you&#39;re going to throw that whole balance that we talked about off you&#39;re going to throw off the equilibrium potential for potassium which means you&#39;re going to throw off the resting potential and you&#39;re going to have all sorts of problems so let&#39;s break down what a potassium channel is at the molecular level and let&#39;s see what happens if you mess with it so as I already mentioned there&#39;s many types of potassium channels okay um based on their structure right based on whether they&#39;re ligand gated whether they&#39;re mechanically gated voltage-gated Etc but in general potassium channels are made up of four protein subunits four subunits we can see that here okay those four subunits come together and they form a poor a poor a poor is something which things can flow in and out of if this was a leak potassium channel that poor would always be open right if it was a ligandicated Channel or a voltage-gated channel sometimes the pore would be closed off inside the pore there&#39;s something which is called a selectivity filter a selectivity filter and it is shaped in a certain way and it has a certain distribution of charges such that it is selective for certain types of ions potassium channels have a selectivity filter which is governed by a poor Loop which is selective for potassium it only lets potassium in and out it doesn&#39;t let other things in and out okay uh the way that the the the the structure of potassium channels was discovered was by utilizing scorpion toxin so applying it to cells and it was found that scorpion toxin blocks uh potassium channels I believe it blocks all of them so it binds to the poor and it&#39;s kind of like somebody&#39;s shoved gum in it okay and it just blocks it off so potassium can&#39;t flow well that&#39;s going to cause all sorts of problems isn&#39;t it it&#39;s going to prevent uh the potential uh changes in resting potential from occurring and it&#39;s going to lead to take a moment pause the lecture and think about this okay your your potassium channels are blocked but your sodium potassium pump is still working what&#39;s that mean it&#39;s constantly bringing a little bit of potassium in well guess what if you block the leak potassium channels potassium is coming in potassium is coming in the pump keeps bringing it in bringing it in bringing it in it&#39;s going to keep building up building up building up building up and that&#39;s going to increase the voltage potential of the cell so the cell is not going to be able to maintain its state of rest well eventually that&#39;s going to cause problems because the cell is going to Fire and Fire and Fire and Fire and until it can&#39;t fire anymore and it dies so this is one of the ways in which we can imagine scorpion toxin leads to death it um it prevents your nervous system from signaling property because it properly because it disrupts the ability for neurons to have a resting state we&#39;ll find that other toxins in animals like uh snake venom spider Venoms puffer fish they tend to block other types of channels usually sodium channels uh and the idea is the same you are disrupting a neuron&#39;s ability to do what it wants to do when you disrupt sodium channels you&#39;re usually disrupting its ability to fire an action potential so you&#39;re disrupting its ability to send a signal maybe to send a signal to the heart to tell it to beat to the lungs to tell them to breathe right here we&#39;re kind of seeing the opposite we&#39;ve blocked potassium channels and so we can&#39;t maintain the resting state so the neuron it raises up raises up and fires until basically it runs out of energy and dies okay uh let&#39;s talk about some other aspects of potassium channels here so this was a mouse model again which was developed in the study of potassium channels called the Weaver Mouse Weaver and it was called Weaver because they found when they were messing around with the structure of these potassium channels that these mutant mice which they had generated these chin they&#39;re called transgenic they&#39;ve introduced um or a change in the gene of the animal that codes for potassium channels in this case they uh had an unsteady gait okay so they were unsteady on their feet they kind of weaved you know they were they had what we would call ataxia and uh as it was found that this particular mutation the Weaver mutation is associated with a change in potassium channels specifically in the cerebellum we&#39;re going to learn about the cerebellum later in this course it&#39;s an area of the brain which is no surprise It&#39;s associated with balance um and the change was such that it altered the selectivity filter of the potassium channels by changing the shape of the poor Loop it changed the shape of the poor Loop so that it was no longer as selective as it used to be it used to be that the poor Loop was only selective to potassium now in this model the Weaver mouse that poor Loop is selective not just to potassium but to sodium as well so think about this logically take a moment pause the lecture what&#39;s that going to cause how&#39;s that going to change the electricity of the cell remember there&#39;s very little sodium inside the cell when the neuron is at rest you&#39;ve got leak potassium channels which are open and now we&#39;ve got an animal model in which those leaked potassium channels don&#39;t just allow potassium through they also allow sodium through what&#39;s going to happen well it&#39;s a bunch of sodium is going to flow into the neurons it&#39;s going to raise the membrane potential up above where it should be and you&#39;re going to have neurons that have an inability to maintain their resting potential it causes problems in the cerebellum in particular you have a loss of balance and ultimately it leads to early death okay and the cells are going to die and that&#39;s going to cause all sorts of problems we see alterations in potassium channels in certain disorders neurological disorders such as epilepsy epilepsy is associated with uncontrolled neuronal firing in areas like the cortex and one of the ways in which congenital epilepsy uh occurs is through mutations at the level of potassium channels in which they&#39;re not as selective as they&#39;re supposed to be and certain cells uh have difficulty in certain areas maintaining their resting state so they&#39;re more prone to have these chain reactions of firing which causes an epileptic seizure let&#39;s talk about uh again just driving home the importance of potassium to the resting potential why it is that um maintaining an equilibrium of flow of potassium and a state in which there&#39;s more potassium inside than out generally is preferred well keep in mind again you&#39;ve got leak potassium channels all over the neuron the resting potential for the neuron as I said it&#39;s usually close to e sub k e sub K means the equilibrium potential for K potassium okay it&#39;s close to this because the membrane is relatively permeable to potassium so potassium is leaving it&#39;s getting brought in a little bit and that flow is generally equivalent now the membrane potential is sensitive to the amount of extracellular potassium that is present at any given time remember normally there&#39;s very little extracellular potassium present in the extracellular fluid if you alter that by say injecting something like calcium chloride into somebody you give them an injection of it and you raise the level of calcium or I&#39;m sorry potassium I think I said calcium chloride I apologize everybody I meant potassium chloride and you raise the level of potassium in the extracellular fluid this is a problem why because now you might have more potassium in the extracellular fluid than you do in the intracellular fluid well the potassium is going to want to move through those leak potassium channels in that case so we can see here if you as you increase the amount of extracellular potassium this K plus sub o okay that&#39;s referring to potassium outside the cell if you raise it usually it&#39;s sitting at about five millimolars if you raise it by 10 fold from 5 to 50 millivolters you see a massive change in VM what does VM mean v stands for voltage sub m stands for membrane so VM is the membrane potential of the neuron we see a massive change in the neuron&#39;s membrane potential at rest from around negative 65 to negative 17 millivolts it raises it you can see that here as the extracellular millimolar concentration of potassium increases so too does the membrane potential if you inject a large amount of potassium chloride it will lead to Cardiac Arrest okay in an individual because there is an inability to regulate the resting potential that leads to Cardiac Arrest similar to what we were talking about with scorpion toxin or with the Weaver Mouse right all these different things lead to an inability to regulate the resting potential potassium key player here we&#39;re raising extracellular potassium levels it leads to a failure to regulate the resting potential leads to death so extracellular potassium levels are super important right uh obviously we don&#39;t want them getting too high because that&#39;s going to cause a problem we want to keep them at that low-ish level how does the brain do this right because you&#39;re taking in potassium throughout the day you know you eat a banana lots of potassium in there you might drink some Gatorade something with various electrolytes okay that&#39;s that&#39;s typically that&#39;s reflecting sodium electrolytes right um other things right through our diet right changing these concentrations throughout the day okay number one the blood-brain barrier what is the blood-brain barrier well we know that the brain needs blood okay right because the blood carries glucose all these sorts of things okay but there is a barrier uh here in the walls of the capillaries which are carrying the blood and this blood-brain barrier it&#39;s really important for a number of different things its real function is it prevents toxins or chemicals from the periphery again you&#39;re taking things into your body all the time via your diet Etc it prevents certain things of certain sizes certain charges from Crossing into the brain from the blood into the brain so it&#39;s one way the brain protects itself from from from toxins in the periphery one of the other things it does is it limits the movement of potassium ions into the brain so this helps restrict the amount of potassium in the extracellular fluid and the second important thing are our good friends astrocytes remember astrocytes are those star-shaped glial cells and we said that one of the things that they do is they take up nutrients from the extracellular fluid and they help provide those to neurons the other thing that they do is they buffer the amount of potassium in the extracellular space okay so if there&#39;s too much potassium in the fluid they&#39;ll take some of it up into themselves to lower those levels so uh the other thing that occurs here okay the third Factor we&#39;ve got blood brain barrier limiting the movement of potassium ions into the the blood that flows to the brain astrocytes will take up some potassium to lower it in the fluid and then finally we have what&#39;s called spatial buffering spatial buffering there&#39;s a lot of extracellular fluid okay there&#39;s cerebral spinal fluid Etc and it&#39;s dissipated over a large space so this spreads the potassium out again helps to keep that concentration around about five millimolars that&#39;s the magic number we want all right that was a big one a big lecture on the resting potential here a lot of information uh I know it might seem overwhelming at this point but take your time watch that resting potential summary video I believe it&#39;s about five minutes uh in the module one section under this lecture and after you&#39;re done try to think about try to explain right in your notes try to write a response what is diffusion what is electrostatic pressure how do these two forces interact Define them but also talk about how they interact how is the sodium potassium pump involved how are the leak potassium pumps involved right what is it that contributes to the resting potential what are the forces what is the flow the gradient of ions underlying that resting potential okay uh we&#39;ll see you next time for our next lecture which will be on the action potential so we&#39;ve talked about the neuron at rests now we&#39;re going to talk about when the neuron is not at rest when it&#39;s coming out of that state

all right everybody so in this lecture up to this point now we we&amp;#39;ve kind of discussed the gross anatomy of neurons uh we&amp;#39;ve discussed other cells in the brain glial cells uh and just basically how it is that they differ physically in in terms of their their size their shape and their parts from the other types of cells that we find throughout the body in this lecture we&amp;#39;re going to start to get into the ionic basis of what it is that makes them excitable cells and there&amp;#39;s two components of that the first of which is the resting potential the neurons spend the majority of their time at rest and the second of which is the action potential which we&amp;#39;ll cover later before we jump into that I do want to mention really quickly if you&amp;#39;re looking on the canvas under the modules section after certain lectures you can see I&amp;#39;ve got the PDFs of the slides there for you to study without having to go back and listen to the whole lecture again but in addition to that occasionally you will see practice games using Materia and there there are some practice games for the resting potential the action potential Etc you are not required to complete these but they do um students do find them useful in terms of helping to study and helping to to practice these Concepts so I encourage you to check those out uh let&amp;#39;s begin then so our goals for today uh uh is to discuss what it means for a neuron to be at rest what contributes to that and we&amp;#39;ll find that that has to do with some unique proteins at the level of the phospholipid bilayer the membrane uh we&amp;#39;ll talk about ionic concentrations and we&amp;#39;ll talk about channels um and uh and how that they how they affect these things and and contribute to the state in which the neuron is not communicating with other neurons so let&amp;#39;s begin here uh the study of some of these processes that we&amp;#39;re going to talk about really could be grouped within as I mentioned I think in the first lecture there&amp;#39;s there&amp;#39;s many subfields of Neuroscience and uh this particular sub-discipline or or sub area of study would be referred to as neurophysiology so we&amp;#39;re looking at how it is that the processes within cells both electrical and chemical uh their makeup their physical makeup Etc uh govern their ability to Signal okay so as I say we&amp;#39;re talking about the resting potential today the opposite component to that is the action potential the action potential is when the neuron actually rapidly sends an electrical signal an electrical signal travels down its axon and then it sends a message typically a chemical message across the synapse to another neuron as I said though the majority of a neuron&amp;#39;s lifespan is spent at rest technically uh so action potentials are very brief blips in changes in the membrane potential don&amp;#39;t worry we&amp;#39;ll explain what a membrane potential is but again the majority of the time it is at rest uh We&amp;#39;ve covered what neurotransmitters are in the previous lecture we&amp;#39;ve covered what synapses are um and so now we&amp;#39;ll see just essentially again what is the neuron doing when it&amp;#39;s not signaling so to introduce this concept I want to kind of drive home the uh the importance of what it is that we&amp;#39;re talking about here and that has to do with electricity what makes neurons special is that they have this ability to store and release electrical charge in the form of different different manners right but in a sense they are little batteries right that&amp;#39;s that&amp;#39;s what uh that&amp;#39;s what that&amp;#39;s what it means to store and release electrical charge this is a very special process so I want to just get us prepared for that aesthetically uh with a with a clip from one of the greatest films of all time here battery and over 25 000 and 18 years combined with a form of fusion the machines had found all the energy they would ever need a field endless feelings for human beings are no longer born [Music] for the longest time I wouldn&amp;#39;t believe it and then I saw the fields watch them liquefy the dead so they could be fed intravenously to be standing there facing the pure horrified precision I came to realize the obviousness of the truth what is the Matrix control The Matrix is a computer-generated Dreamer built to keep us under control in order to change the human being into this no I okay so we&amp;#39;re thinking about batteries here we&amp;#39;re going to be thinking about electricity quite a bit uh as we move forward and again the metaphor I think will hold that neurons themselves are very much like batteries we&amp;#39;re going to break down the different components of electricity that govern these properties here in a little bit but first let&amp;#39;s talk about our cast of chemicals that are involved and beginning at the level of ions Okay so when the neuron is at rest the resting potential itself is reflecting this balance between various electrochemical forces particularly diffusion and electrostatic pressure these are the result of ionic concentrations so we all know that cells have an intracellular fluid which is separate from the extracellular fluid the outside area and it&amp;#39;s separated by this lipid membrane we&amp;#39;re going to talk about that in a little bit we&amp;#39;ll expand on that but in particular what makes this special is that the fluid on the inside of the cell and on the outside of the cell differs slightly in terms of the ions or at least the amount of ions that are within it particularly the distribution of what are called anions and cations anions are negatively charged cations are positively charged okay so there are four of which that are the most common that we&amp;#39;re going to talk about throughout this semester and those would be sodium potassium chloride and calcium so note all but one of those is a cation is positively charged uh chloride is an anion it is negatively charged we&amp;#39;ll talk about that when we talk about gaborergic neurons later but the distribution of these anions and cations uh between the two spaces the difference in that distribution is what contributes to electrical charge or electrical potential the difference in charges and don&amp;#39;t worry if you&amp;#39;ve never taken you know a physics class where they&amp;#39;ve broken down this kind of stuff we&amp;#39;re going to get through it we&amp;#39;re not going to get lost in the weeds our goal here is to understand the the electrical component of this enough that it serves us to understand how to work with the cells um so as I mentioned ions are dissolved throughout fluid in the body okay there are ions in the extracellular fluid and there are ions in the intracellular fluid and they&amp;#39;re separated by the membrane of the cell now one of the things that we&amp;#39;re going to find that&amp;#39;s special about neurons is that they have unique a unique cast of proteins throughout their membrane which form like Gates which can open and close and allow in and out the flow of certain ions and that ultimately is what allows the neuron to transition from one level of voltage or potential to another the resting potential to the action potential so let&amp;#39;s review our phospholipid membrane everybody here in this class has had your biology prerequet at this point and certainly I think um this is probably review and that you you understand what the phospholipid membrane is but let&amp;#39;s go through it really quickly and then we&amp;#39;ll learn how neurons can break some of the rules here so uh this in particular the phospholipid membrane right we&amp;#39;re dealing with aspects of molecules that are hydrophilic which means they um they do not repel water okay they&amp;#39;re water loving quote unquote they dissolve in water and so our ions are hydrophilic they dissolve in water um and then we have our hydrophobic compounds which are water fearing they do not dissolve in water they repel water and again at the level of the chemistry this is due to differences in electrical charge we&amp;#39;re not super worried about that here you can think more about that in a chemistry class uh but let&amp;#39;s just state that lipids right fatty lipids are hydrophobic okay this is why if you put olive oil in water it floats right the little the you&amp;#39;ll see the beads of the olive oil floating and through the water because the olive oil is a lipid it is hydrophobic okay so the membrane of neurons and indeed all cells is composed of these long nonpolar chains of carbon binded to hydrogen bonded to hydrogen which we refer to as phospholipids and the phospholipid bilayer itself is arranged in such a way that you have these polar heads okay uh facing outward toward the extracellular fluid and toward the intracellular fluid which are hydrophobic and the tails are arranged forming the inner component of the layer uh facing toward each other which are nonpolar okay and hydrophilic so this is the extent of which you need to know there again we&amp;#39;re not super concerned with the biochemistry in this but just the takeaway is that we have a membrane which is keeping the extracellular fluid out from the intracellular fluid and we&amp;#39;re going to find that the membrane has special proteins that act like gates in it which can briefly allow this to change so what are these special proteins okay well they are some of them are called ion channels in fact today with what we&amp;#39;re talking about in regards to the resting potential ion channels are the most important component for maintaining the resting potential so these are proteins which span the membrane let me get my laser pointer out here we can see our phospholipid membrane and here we have this protein which is composed of you know different polypeptide subunits okay and part of the this this protein is is facing outside of the membrane part of it is inside the membrane so we say it is membrane spanning okay so here it is and this is an ion Channel it is a special type of protein which can open up and allow the flow of certain ions from outside of the cell into the cell and in some cases it can allow the flow of certain ions from inside of the cell to go outside of the cell so they are specialized these proteins in the way that they&amp;#39;re made up their charges Etc are specific in such a way that they only allow certain ions to flow through them so there are different types of of ion channels um and in response to how it is that they open or close they require different types of stimuli so we call these gated ion channels and they can open or close in response to changes in voltage that would be called a voltage-gated ION channel and so that would open or close if the voltage of the neuron rises above a certain point or dips below a certain point that will automatically open or close a voltage-gated ION channel um there are chemically gated ion channels which we call ligand gated ion channels a ligand in biology is just a molecule which binds with a substrate okay it&amp;#39;s like a key that fits into the lock in a door okay neurotransmitters are ligands all right so sum gated ion channels are opened by chemicals by neurotransmitters like a key going into a lock and opening the door some of them are open and closed in response to Mechanical action so we&amp;#39;ll see that there are ATP powered pumps like the sodium potassium pump and this opens and closes mechanically and is powered by ATP and it allows sodium and potassium to flow through it there are other types of membrane spanning proteins forming channels okay that we&amp;#39;re going to talk about later in this course uh things like G protein coupled receptors okay they&amp;#39;re a little bit more complex in the way that they work so we&amp;#39;re going to focus on those later when we talk about neurotransmitter systems but for today we&amp;#39;re really going to focus on voltage-gated ION channels and the sodium potassium pump so ah let&amp;#39;s talk about the ionic concentrations of a typical neuron inside the cell versus outside of the cell so the Hallmark of the neuron at rests is that it contains this large amount of negatively charged proteins take a look here negatively charged proteins inside of the neuron okay so these are the things inside the cell you know making up stuff like I don&amp;#39;t know the endoplasmic reticulum uh Golgi apparatus all that kind of stuff that you already are familiar with right these are overwhelmingly negatively charged and they&amp;#39;re large so this means first off you&amp;#39;ve got a net negative charge inside the neuron generally due to all these large negatively charged proteins comparatively outside the cell the extracellular space extracellular fluid there are very few negatively charged proteins okay so that&amp;#39;s our first difference extracellular fluid tends to be more positively charged than the interior fluid of a neuron and one of the big reasons for that is because the interior of the neuron has all these large negatively charged proteins in it but what about ionic concentrations well here we see some differences as well outside the neuron in the extracellular fluid there&amp;#39;s a whole lot of positively charged sodium ions and there is a small small number of positively charged potassium ions inside the neuron there is a very small amount of positively charged sodium ions and a relatively large amount of positively charged potassium ions however that is not enough to overcome the net negative charge of all the negative proteins inside there so we&amp;#39;ll come to find that when the neuron is at rest it has a net negative charge typically around negative 65 millivolts okay and for the neuron to send a chemical message when it leaves the resting potential it&amp;#39;s moving away from negative 65 and eventually up into the positive in order to do that what&amp;#39;s going to happen is that we need to shift the balance of these ionic concentrations generally we need to bring more sodium into the cell to help raise that potential up in the positive direction there don&amp;#39;t worry about that just yet but just kind of be thinking about the distribution of charges let&amp;#39;s break down electricity really quickly the major components that we&amp;#39;re concerned about here all right and again we have our our analogy of the battery okay and uh a battery is something through which current can flow current is the movement of electrical charges it&amp;#39;s measured in amps so electrical current is really just reflected electrical charge movement of electrical charge is just reflecting in any case in a battery whatever movement of ions okay because ions are positively or negatively charged their movement that is movement of electrical charge okay electrical potential that that&amp;#39;s the term that we use in Neuroscience frequently is we&amp;#39;ll refer to a membrane potential and action potential a resting potential we use potential synonymous with voltage okay voltage is the force which is being exerted on a given particle at a given time and it&amp;#39;s measured in volts okay it&amp;#39;s due to the difference between the anode and cathode regions which are positively charged regions and negatively charged reasons regions okay so if you had a battery okay with an ant with an anode and a cathode end that&amp;#39;s suggesting that on the one end of the battery there are more positively charged ions and on the other end there are more negatively charged ions and the difference between these two the larger the difference between them creates a larger potential a potential for like energy you can even think about really and that potential is the voltage the larger the potential the more Force there is to move those ions if necessary Opposites Attract remember that okay you got a lot of positive charge one way and a lot of negative charge one way what happens okay well they want to come together there&amp;#39;s a lot of energy trying to push them together strong magnets are like this right trying to pull them together rather that&amp;#39;s almost analogous to what we&amp;#39;re talking about here let&amp;#39;s talk about conductance conductance conductance is the relative ability of an electrical charge to move from one point to another it&amp;#39;s measured in Siemens okay and conductance is the inverse of resistance resistance the relative inability of an electrical charge to move from one area to the other this is measured in ohms so we&amp;#39;ll find particularly that resistance and conductance are important when we consider axons later when we&amp;#39;re talking about the action potential how is electricity kept inside the wire right how does it flow how does it move there&amp;#39;s a certain amount of resistance that&amp;#39;s involved right keeping it flowing along almost like a tube of toothpaste being squeezed through there down the wire we&amp;#39;ll get into all that later all of these components come together to form something called Ohm&amp;#39;s law Ohm&amp;#39;s law Ohm&amp;#39;s law states that current I is equal to conductance multiplied by voltage that&amp;#39;s what gives you current okay now we don&amp;#39;t want to get too lost in these but for the exam you should know you should be able to Define potential and voltage what is that well it&amp;#39;s the force exerted on a particle she able to Define conductance it&amp;#39;s the ability of a particle to move Define resistance it&amp;#39;s the inability of a particle to move to find current all of these they might sound like a bunch of of the gobbledygook right now but when we start to talk about changes in the potential of the neuron you&amp;#39;re going to start thinking about these in your head and they&amp;#39;re going to come together and they&amp;#39;re going to make sense I promise all right back to the resting potential I kind of already gave this away on the last slide we said that when a neuron is at rest when it&amp;#39;s inactive it&amp;#39;s not doing anything it&amp;#39;s typically sitting at about negative 65 millivolts Okay negative 65 millivolts that number that potential is a reflection of the difference in charge on of the ionic concentrations on the inside of the neuron versus the outside of the neuron how do we know this well if you were to use a a reference electrode and you were to place on a reference electrode uh let&amp;#39;s say onto the axon of a neuron okay you place it inside there so that it&amp;#39;s sampling the electricity in the intracellular fluid you then take another electrode and you place it outside of the neuron and you measure the uh electricity in that fluid the the potential in that fluid okay the difference between those numbers is what shows up as our potential and that&amp;#39;s negative 65 when the neuron is at rest so a lot of negatively charged proteins inside the neuron at rest a little bit of sodium a lot of potassium outside the neuron lots of positively charged sodium a little bit of positively charged potassium no or very few negatively charged proteins and so you have a situation where one number the outside is going to be higher than the inside number which creates a difference and it kind usually winds up being around negative 65 now um we say that this is an average at rest okay in reality that number will fluctuate based on events things like the movement of the sodium potassium pump Etc typically in an average neuron it&amp;#39;ll fluctuate between negative 50 to negative 80 millivolts and so we say the average resting potential is negative 65. this is in the beginning of the course um we try to stick with an average number but we&amp;#39;ll find later on in this course that some neurons break this Rule and have a different average resting potential and they tend to be specialized neurons in areas of like sensory systems so involved in like the ear or the eye but overwhelmingly in terms of neurons in the brain we&amp;#39;re seeing this negative 65 average okay and that that resting potential that average is a reflection of fluctuations moving between negative 50 to negative 80 millivolts so here we have our membrane and we&amp;#39;ve talked about at this point that there are certain membrane spanning proteins which we call ion channels and they are permeable to specific types of ions some of them are permeable to potassium some are permeable to sodium and we&amp;#39;ll find throughout this course there&amp;#39;s a great deal of variability uh in terms of what it is that they&amp;#39;re permeable to today the most important ones we&amp;#39;ll talk about are sodium and potassium channels now when the neuron is sitting at rest the majority of these ion channels in the membrane are closed the majority are closed okay this makes sense uh the neuron sitting there it&amp;#39;s not doing much and so the gates are closed it&amp;#39;s at rest it&amp;#39;s not taking any visitors today the gates are closed right if the gates were to open that would cause a change in flow of ions and likely cause them the neuron to move away from the resting potential so most of the gates are closed there is however a small small small proportion of potassium channels that are special potassium channels that are always open they never close they&amp;#39;re always open these are called leak potassium channels leak potassium channels so they are leaky they are constantly allowing potassium to flow in and out of the cell okay in small amounts that&amp;#39;ll be important later when we talk about the sodium potassium pump remember that there is a lot of potassium ions inside the cell at rest and relatively few outside the cell we&amp;#39;ll come back to this here shortly foreign so I mentioned this earlier right the neuron at rest the resting potential that difference in potential charges is reflecting a balance between two different forces one of which is diffusion and the other witches of which is electrostatic pressure let&amp;#39;s talk about diffusion diffusion is the idea that uh ions want to diffuse or flow down their concentration gradient okay what does that mean well let&amp;#39;s look at this image on the bottom left here if you take a cup of water and you drop food coloring a single drop of food coloring into the water what happens okay the single drop of food coloring is highly highly concentrated it contains many many many molecules of this particular coloring which are concentrated in a small tight space when it hits the water it spreads out it diffuses those molecules spread throughout the medium of the water they move from an area of high concentration to an area of low concentration they spread out they diffuse okay uh another way to think about this is like being in a crowded elevator you walk into the elevator there&amp;#39;s a bunch of people already in there boy you don&amp;#39;t want to be in there it&amp;#39;s claustrophobic you can&amp;#39;t wait to just get out you want to diffuse down your concentration gradient out into the Hall where there&amp;#39;s people are more spread out and you don&amp;#39;t feel so crammed together that&amp;#39;s diffusion okay and we see another example of that in this figure here okay tight concentration of these little beads in this cup you pour it into a bigger area like the hallway I was mentioning and they spread out okay they spread out across their concentration gradient so uh diffusion is the idea that ions want to move from areas in which they are crowded which there are many of them concentrated to areas where they are less concentrated so uh let&amp;#39;s take a look at how diffusion works with these uh membrane channels okay or semi-permeable member the semi-permeable membrane we call it the membrane semi-permeable right because it has channels in it that can open and close right and so sometimes it&amp;#39;s permeable sometimes it&amp;#39;s not right so membrane permeability it changes right depending on what&amp;#39;s going on with the neuron depending on how many gates are opened or closed depending on what kind of gates are opened or closed whether they&amp;#39;re potassium Gates sodium Gates whatever right that alters the membrane permeability okay so here in this image in the bottom portion you can see that let&amp;#39;s take a look here we have a few a couple different types of channels let&amp;#39;s imagine we&amp;#39;ve got a semi-permeable membrane separating uh the fluid in this cup we&amp;#39;ll call it separating the fluid on the left from the fluid on the right and there&amp;#39;s two different types of beads in here we&amp;#39;ve got these blue beads and these red beads okay red beads are larger than the blue sure uh we&amp;#39;ve got three channels in the membrane two of these channels are selectively permeable to blue beads to blue beads and so blue beads are free to flow across the membrane and diffuse uh along their concentration gradient and you can see that here there&amp;#39;s an even concentration of blue beads on the left and the right side because they&amp;#39;ve been flowing through those channels if there was more blue beads on the left they would flow through until it was evenly dispersed with the left and the right note that this channel on the middle though is closed and it is impermeable to the red beads we&amp;#39;ll say it&amp;#39;s closed it&amp;#39;s impermeable to the red beads in this state so the red beads stay on the left side they can&amp;#39;t move they might want to move and diffuse but they can&amp;#39;t because the channel the gate doesn&amp;#39;t allow them through and so here in this instance in this example we might imagine that the channels which are open and allowing those blue beads through are are our leak potassium channels that are remaining open that are allowing them to flow in this case now you may be thinking well hey wait a minute uh if there&amp;#39;s a lot of potassium inside the cell and a little bit outside the cell why doesn&amp;#39;t the potassium flow completely down its concentration gradient so that there&amp;#39;s an equal amount of potassium inside and outside we&amp;#39;re going to talk about why that is here shortly if you&amp;#39;re thinking along those lines though good job that&amp;#39;s uh that&amp;#39;s thinking and paying attention to the details and I promise it&amp;#39;ll make sense here shortly before we get to that though let&amp;#39;s talk about our second force that matters electrostatic pressure okay electrostatic pressure this is that simple concept that you all learned in grade school when you were learning to play with magnets okay you learned that Opposites Attract and likes repel that is electrostatic pressure it&amp;#39;s due to the distribution of charges if you have a lot of positive charge on one side and a lot of positive charge on the other and you try to bring them together they&amp;#39;re going to be forced apart they&amp;#39;re going to want to go away from each other if you have a lot of positive charge on one side a lot of negative charge on the other they&amp;#39;re going to want to come together and if you resist that coming together with your hands say you&amp;#39;ve got two strong magnets and you&amp;#39;re physically holding them so that they&amp;#39;re apart they want to come together but you&amp;#39;re holding them apart it takes a certain amount of force resistance on your part to do that that&amp;#39;s analogous to again a potential right the amount of voltage there right the stronger it is the stronger the difference in charge between those two the stronger the potential the stronger the voltage the harder it is for you to resist and keep those magnets apart okay so our third key player here that is involved in maintaining the balance between electrostatic pressure diffusion it&amp;#39;s maintaining a balance of charges a balance of flow of ions is the sodium potassium pump okay it pushes sodium out of the cell and it brings potassium into the cell this is that key point where if those of you in the previous slide were thinking hey if the leaked potassium channels are always open why doesn&amp;#39;t all the potassium just flow right on out of the cell until it&amp;#39;s equivalent with the potassium on the outside well here&amp;#39;s your answer okay the answer is that potassium is Flowing out of the leak potassium channels a little bit at a time because there&amp;#39;s not a lot of them but it is Flowing out a little bit at a time constantly but the actions of the sodium potassium pump are constantly bringing some potassium back into the cell so some potassium is leaving and at the same time some potassium is being brought back in this maintains that difference where you&amp;#39;ve got more potassium inside relative to the outside take a closer look at that here&amp;#39;s our sodium potassium pump and what it&amp;#39;s doing specifically it&amp;#39;s always operating at a consistent rate it&amp;#39;s powered by ATP and what it&amp;#39;s doing is it pumps two potassium ions into the cell for every three sodium ions that it kicks out of the cell now what does that mean it means that the actions of the sodium potassium pump are going to help to yield and maintain that net negative charge inside the cell it&amp;#39;s bringing less positivity in for the amount of positivity it&amp;#39;s kicking out it kicks three positive sodium ions out for every two potassium positive ions it brings in meanwhile leak potassium channels are open and some amount of potassium is always trying to leave down its concentration gradient this constant movement reflects a balance and it builds up a fluid equilibrium which is close to the equilibrium potential for potassium that means that the amount of potassium flowing out is equivalent to the amount being brought in at any given point in time the resting potential is usually very close to the equilibrium potential for potassium we&amp;#39;ll talk more about that in a little bit let&amp;#39;s talk about though why it is or how it is that the neuron fluctuates between about negative 50 to negative 80 millivolts okay it moves like like a needle on a dial kind of back and forth it&amp;#39;ll go down all the way maybe to negative 80 and then it&amp;#39;ll go up up up up up up up up closer to negative 50 and then it&amp;#39;ll go back down down down down down why is that happening well let&amp;#39;s think about this in conjunction with the leak potassium channels and the sodium potassium pump all right you get a lot of large negatively charged proteins inside the cell okay here they are in Gray all right cells got a net negative charge you&amp;#39;ve got a lot of potassium inside the cell all right the sodium potassium pump is bringing more potassium in and as potassium keeps building up building up building up building up inside the cell what&amp;#39;s going to happen well as it gets to be more and more crowded inside the cell there&amp;#39;s more and more potassium and those leak potassium channels are staying open what&amp;#39;s going to happen diffusion is going to cause more and more of those potassium ions to leave so this is how you get that fluctuation between negative 50 to negative 80. okay at negative 50 there&amp;#39;s probably more potassium ions inside the cell uh and then what happens is they begin to diffuse out more rapidly out out out out and you see the the cell go from negative 50 down to negative 60 to negative 65 to 70 to 80. well now there&amp;#39;s not as much potassium anymore so diffusion has slowed down there&amp;#39;s not much potassium leaving because because there&amp;#39;s not much in the in the cell so it doesn&amp;#39;t want to diffuse right it&amp;#39;s not as crowded anymore well the sodium potassium pump this whole time is bringing more potassium in eventually it&amp;#39;ll begin to build back up build back up build back up and then it&amp;#39;ll begin to diffuse out more rapidly all right so that&amp;#39;s how the leak potassium channels in conjunction with the sodium potassium pump create this ebb and flow between neg 50 to neg 80 and this is how we wind up with our average resting membrane potential around negative 65 millivolts we&amp;#39;re sitting at rest here in the coming lectures we&amp;#39;ll find that when we move past negative 50 something special occurs keep in mind too we&amp;#39;re always kicking out three sodium ions at rest again making sure that there&amp;#39;s very little sodium inside the cell helping to maintain a net negative charge so this slide is reviewing everything that I just said here right so as the cell becomes more positive it becomes more crowded the potassium sodium potassium pump has brought more potassium in potassium will begin to diffuse out the leak potassium channels down its concentration gradient okay but what about after a bunch of potassium has diffused out maybe the cells down to about negative 80 millivolts now now what&amp;#39;s going to happen well now our second force is going to act electrostatic pressure the cell has become more and more negative inside and you&amp;#39;ve got a lot of positivity outside the cell well the more negative the cell is the more that positivity wants to get in right Opposites Attract electrostatic pressure and well how is that positivity going to get back in the cell some of it&amp;#39;s coming in through the sodium potassium pump but very little a little at a time slowly okay what&amp;#39;s the other thing the way that this could occur let&amp;#39;s imagine that we&amp;#39;re not talking about any other Gates being open we&amp;#39;ve just got our leak potassium channels open okay well guess what uh if it&amp;#39;s really negatively charged inside uh then that pull Opposites Attract those positively charged potassium ions are going to want to come back in right because they&amp;#39;re attracted to that an area of negativity okay so electrostatic pressure will bring potassium ions back in through the leak potassium channels eventually they&amp;#39;ll build up build up due to the actions of electrostatic pressure but also the sodium potassium pump and then they&amp;#39;ll diffuse back on out again it&amp;#39;s a constant ebb and flow back and forth yeah all right so again this ebb and flow this balance between the force of diffusion and electrostatic pressure and if you guys are taking notes Here an easy way to remember this diffusion is typically talking about ions diffusing and leaving the cell okay leaving down their concentration gradient moving from a crowded area because the intracellular space that&amp;#39;s like the elevator right it&amp;#39;s small it&amp;#39;s crowded to a large less crowded area the extracellular space diffusion leaving the inside of the cell going to the outside electrostatic pressure though is about things being brought in from the outside to the inside right keep that in mind it&amp;#39;s an easy way to remember the difference between those two let&amp;#39;s talk about the equilibrium potential really quickly here I mentioned this earlier we said that at rest the neuron uh its membrane its resting membrane potential is typically quite close to what we refer to as the equilibrium potential for potassium what is the equilibrium potential it is the point at which the flow of a given ion is equivalent in both directions meaning that you have a balance between the amount of the ion that is leaving and the amount of the ion that is being brought in okay the equilibrium potential for potassium would mean that there is an equivalent amount of potassium in terms of charge leaving as is entering right in reality the resting membrane potential is going to fluctuate up and down as we said and it&amp;#39;s going to move closer to the equilibrium potential for potassium and then move away from it that&amp;#39;s usually what&amp;#39;s happening okay now the equilibrium potential can be calculated for all sorts of different ions okay not just potassium but sodium other things too right uh you can use an equation to calculate this called the nernst equation now the nernst equation I&amp;#39;m not going to ask you guys to derive that I don&amp;#39;t think it&amp;#39;s useful for you in this course but just know that what it&amp;#39;s taking into account is um the potential um that would be needed in terms of balancing the force the voltage to push a single ion across the membrane at a given time relative to those leaving okay so it&amp;#39;s going to take into account things like resistance of the membrane which is going to be governed by the amount of channels that are opened or closed okay it&amp;#39;s taking into account conductance all those sorts of factors and so the nernst equation can calculate the equilibrium potential for a single ion there are other equations in neurophysiology used as well which can calculate the equilibrium potential of permeability for multiple types of ions and this is more accurate to reality because in reality the membrane is permeable to more than just one ion okay it&amp;#39;s permeable to more than just potassium it also has areas that are permeable to sodium or or maybe calcium or any other number of ions in order to calculate all of these permeabilities at once to to come up with an equilibrium potential you use something called the Goldman equation again I&amp;#39;m not going to make you all derive that but just understand that it&amp;#39;s a reflection of the resistance of the membrane how many gates are opened versus how many are closed uh these sorts of things okay so for my purposes for the exam it&amp;#39;s enough for you to just know what the nernst equation is what the Goldman equation is what the equilibrium potential is how the equilibrium potential is related to the resting potential and particularly how&amp;#39;s it related to the action or to the flow of potassium how does that relate to leak potassium channels and how does it relate to the sodium potassium pump I have here I&amp;#39;m not gonna go through this video uh in the in the lecture since this is recorded but I have posted this video in the uh modules section underneath this lecture okay it&amp;#39;s a summary video of everything we&amp;#39;ve just talked about so when you get done watching this video watch this uh little summary it&amp;#39;s a short uh few minute summary of everything I just talked about and it puts all the pieces together uh in to form the resting membrane potential so check that out after this lecture is over okay let&amp;#39;s delve a little bit deeper into uh channels particularly potassium channels why potassium channels because they&amp;#39;re super important and I think I&amp;#39;ve emphasized that at this point that you know potassium channels there&amp;#39;s different types of potassium channels there are voltage-gated potassium channels there are ligand-gated potassium channels but we talked about a special type of potassium Channel today called the leak potassium Channel all neurons have leak potassium channels which are always open now depending on the type of neuron what it&amp;#39;s specialized for it may have more or less leak potassium channels than another uh but all neurons have these okay so potassium channels in terms of gated ion channels or types of ion channels they&amp;#39;re one of the really important ones if you mess with potassium channels you&amp;#39;re going to throw that whole balance that we talked about off you&amp;#39;re going to throw off the equilibrium potential for potassium which means you&amp;#39;re going to throw off the resting potential and you&amp;#39;re going to have all sorts of problems so let&amp;#39;s break down what a potassium channel is at the molecular level and let&amp;#39;s see what happens if you mess with it so as I already mentioned there&amp;#39;s many types of potassium channels okay um based on their structure right based on whether they&amp;#39;re ligand gated whether they&amp;#39;re mechanically gated voltage-gated Etc but in general potassium channels are made up of four protein subunits four subunits we can see that here okay those four subunits come together and they form a poor a poor a poor is something which things can flow in and out of if this was a leak potassium channel that poor would always be open right if it was a ligandicated Channel or a voltage-gated channel sometimes the pore would be closed off inside the pore there&amp;#39;s something which is called a selectivity filter a selectivity filter and it is shaped in a certain way and it has a certain distribution of charges such that it is selective for certain types of ions potassium channels have a selectivity filter which is governed by a poor Loop which is selective for potassium it only lets potassium in and out it doesn&amp;#39;t let other things in and out okay uh the way that the the the the structure of potassium channels was discovered was by utilizing scorpion toxin so applying it to cells and it was found that scorpion toxin blocks uh potassium channels I believe it blocks all of them so it binds to the poor and it&amp;#39;s kind of like somebody&amp;#39;s shoved gum in it okay and it just blocks it off so potassium can&amp;#39;t flow well that&amp;#39;s going to cause all sorts of problems isn&amp;#39;t it it&amp;#39;s going to prevent uh the potential uh changes in resting potential from occurring and it&amp;#39;s going to lead to take a moment pause the lecture and think about this okay your your potassium channels are blocked but your sodium potassium pump is still working what&amp;#39;s that mean it&amp;#39;s constantly bringing a little bit of potassium in well guess what if you block the leak potassium channels potassium is coming in potassium is coming in the pump keeps bringing it in bringing it in bringing it in it&amp;#39;s going to keep building up building up building up building up and that&amp;#39;s going to increase the voltage potential of the cell so the cell is not going to be able to maintain its state of rest well eventually that&amp;#39;s going to cause problems because the cell is going to Fire and Fire and Fire and Fire and until it can&amp;#39;t fire anymore and it dies so this is one of the ways in which we can imagine scorpion toxin leads to death it um it prevents your nervous system from signaling property because it properly because it disrupts the ability for neurons to have a resting state we&amp;#39;ll find that other toxins in animals like uh snake venom spider Venoms puffer fish they tend to block other types of channels usually sodium channels uh and the idea is the same you are disrupting a neuron&amp;#39;s ability to do what it wants to do when you disrupt sodium channels you&amp;#39;re usually disrupting its ability to fire an action potential so you&amp;#39;re disrupting its ability to send a signal maybe to send a signal to the heart to tell it to beat to the lungs to tell them to breathe right here we&amp;#39;re kind of seeing the opposite we&amp;#39;ve blocked potassium channels and so we can&amp;#39;t maintain the resting state so the neuron it raises up raises up and fires until basically it runs out of energy and dies okay uh let&amp;#39;s talk about some other aspects of potassium channels here so this was a mouse model again which was developed in the study of potassium channels called the Weaver Mouse Weaver and it was called Weaver because they found when they were messing around with the structure of these potassium channels that these mutant mice which they had generated these chin they&amp;#39;re called transgenic they&amp;#39;ve introduced um or a change in the gene of the animal that codes for potassium channels in this case they uh had an unsteady gait okay so they were unsteady on their feet they kind of weaved you know they were they had what we would call ataxia and uh as it was found that this particular mutation the Weaver mutation is associated with a change in potassium channels specifically in the cerebellum we&amp;#39;re going to learn about the cerebellum later in this course it&amp;#39;s an area of the brain which is no surprise It&amp;#39;s associated with balance um and the change was such that it altered the selectivity filter of the potassium channels by changing the shape of the poor Loop it changed the shape of the poor Loop so that it was no longer as selective as it used to be it used to be that the poor Loop was only selective to potassium now in this model the Weaver mouse that poor Loop is selective not just to potassium but to sodium as well so think about this logically take a moment pause the lecture what&amp;#39;s that going to cause how&amp;#39;s that going to change the electricity of the cell remember there&amp;#39;s very little sodium inside the cell when the neuron is at rest you&amp;#39;ve got leak potassium channels which are open and now we&amp;#39;ve got an animal model in which those leaked potassium channels don&amp;#39;t just allow potassium through they also allow sodium through what&amp;#39;s going to happen well it&amp;#39;s a bunch of sodium is going to flow into the neurons it&amp;#39;s going to raise the membrane potential up above where it should be and you&amp;#39;re going to have neurons that have an inability to maintain their resting potential it causes problems in the cerebellum in particular you have a loss of balance and ultimately it leads to early death okay and the cells are going to die and that&amp;#39;s going to cause all sorts of problems we see alterations in potassium channels in certain disorders neurological disorders such as epilepsy epilepsy is associated with uncontrolled neuronal firing in areas like the cortex and one of the ways in which congenital epilepsy uh occurs is through mutations at the level of potassium channels in which they&amp;#39;re not as selective as they&amp;#39;re supposed to be and certain cells uh have difficulty in certain areas maintaining their resting state so they&amp;#39;re more prone to have these chain reactions of firing which causes an epileptic seizure let&amp;#39;s talk about uh again just driving home the importance of potassium to the resting potential why it is that um maintaining an equilibrium of flow of potassium and a state in which there&amp;#39;s more potassium inside than out generally is preferred well keep in mind again you&amp;#39;ve got leak potassium channels all over the neuron the resting potential for the neuron as I said it&amp;#39;s usually close to e sub k e sub K means the equilibrium potential for K potassium okay it&amp;#39;s close to this because the membrane is relatively permeable to potassium so potassium is leaving it&amp;#39;s getting brought in a little bit and that flow is generally equivalent now the membrane potential is sensitive to the amount of extracellular potassium that is present at any given time remember normally there&amp;#39;s very little extracellular potassium present in the extracellular fluid if you alter that by say injecting something like calcium chloride into somebody you give them an injection of it and you raise the level of calcium or I&amp;#39;m sorry potassium I think I said calcium chloride I apologize everybody I meant potassium chloride and you raise the level of potassium in the extracellular fluid this is a problem why because now you might have more potassium in the extracellular fluid than you do in the intracellular fluid well the potassium is going to want to move through those leak potassium channels in that case so we can see here if you as you increase the amount of extracellular potassium this K plus sub o okay that&amp;#39;s referring to potassium outside the cell if you raise it usually it&amp;#39;s sitting at about five millimolars if you raise it by 10 fold from 5 to 50 millivolters you see a massive change in VM what does VM mean v stands for voltage sub m stands for membrane so VM is the membrane potential of the neuron we see a massive change in the neuron&amp;#39;s membrane potential at rest from around negative 65 to negative 17 millivolts it raises it you can see that here as the extracellular millimolar concentration of potassium increases so too does the membrane potential if you inject a large amount of potassium chloride it will lead to Cardiac Arrest okay in an individual because there is an inability to regulate the resting potential that leads to Cardiac Arrest similar to what we were talking about with scorpion toxin or with the Weaver Mouse right all these different things lead to an inability to regulate the resting potential potassium key player here we&amp;#39;re raising extracellular potassium levels it leads to a failure to regulate the resting potential leads to death so extracellular potassium levels are super important right uh obviously we don&amp;#39;t want them getting too high because that&amp;#39;s going to cause a problem we want to keep them at that low-ish level how does the brain do this right because you&amp;#39;re taking in potassium throughout the day you know you eat a banana lots of potassium in there you might drink some Gatorade something with various electrolytes okay that&amp;#39;s that&amp;#39;s typically that&amp;#39;s reflecting sodium electrolytes right um other things right through our diet right changing these concentrations throughout the day okay number one the blood-brain barrier what is the blood-brain barrier well we know that the brain needs blood okay right because the blood carries glucose all these sorts of things okay but there is a barrier uh here in the walls of the capillaries which are carrying the blood and this blood-brain barrier it&amp;#39;s really important for a number of different things its real function is it prevents toxins or chemicals from the periphery again you&amp;#39;re taking things into your body all the time via your diet Etc it prevents certain things of certain sizes certain charges from Crossing into the brain from the blood into the brain so it&amp;#39;s one way the brain protects itself from from from toxins in the periphery one of the other things it does is it limits the movement of potassium ions into the brain so this helps restrict the amount of potassium in the extracellular fluid and the second important thing are our good friends astrocytes remember astrocytes are those star-shaped glial cells and we said that one of the things that they do is they take up nutrients from the extracellular fluid and they help provide those to neurons the other thing that they do is they buffer the amount of potassium in the extracellular space okay so if there&amp;#39;s too much potassium in the fluid they&amp;#39;ll take some of it up into themselves to lower those levels so uh the other thing that occurs here okay the third Factor we&amp;#39;ve got blood brain barrier limiting the movement of potassium ions into the the blood that flows to the brain astrocytes will take up some potassium to lower it in the fluid and then finally we have what&amp;#39;s called spatial buffering spatial buffering there&amp;#39;s a lot of extracellular fluid okay there&amp;#39;s cerebral spinal fluid Etc and it&amp;#39;s dissipated over a large space so this spreads the potassium out again helps to keep that concentration around about five millimolars that&amp;#39;s the magic number we want all right that was a big one a big lecture on the resting potential here a lot of information uh I know it might seem overwhelming at this point but take your time watch that resting potential summary video I believe it&amp;#39;s about five minutes uh in the module one section under this lecture and after you&amp;#39;re done try to think about try to explain right in your notes try to write a response what is diffusion what is electrostatic pressure how do these two forces interact Define them but also talk about how they interact how is the sodium potassium pump involved how are the leak potassium pumps involved right what is it that contributes to the resting potential what are the forces what is the flow the gradient of ions underlying that resting potential okay uh we&amp;#39;ll see you next time for our next lecture which will be on the action potential so we&amp;#39;ve talked about the neuron at rests now we&amp;#39;re going to talk about when the neuron is not at rest when it&amp;#39;s coming out of that state

Transcript for:Neuroscience Lecture: Resting Potential

Transcript for:
Neuroscience Lecture: Resting Potential