hey everyone welcome to professor long flexures in anatomy and physiology as you guys know we're in this coronavirus arachova 19 shutdown and we've moved our classes from face-to-face to online I don't normally teach online which has forced us to find creative ways to deliver information which is why I'm doing this series of videos as you know these videos are all single take done you know very crudely with my laptop I don't have a lot of time to edit or I don't even know how to manipulate the editing software yet I will be doing that in the future so please bear with me for the crudeness of the setup I did get a bigger marker board so I can get more notes in anyway if you are watching this video this is the third number three in this series of my anatomy and physiology part 1 lectures on the nervous system so this is nervous system lecture 3 so if you are in my class you can follow along will be starting somewhere around page 65 and going through the information on the next few pages we're going to be talking about action potentials ion channels and how neurons conduct action potentials and electrical voltage there are two types of excitable cells in the human body excitable cells are those cells which can conduct action potentials have electrical currents flow through the cell the first one we've already talked about which is muscle cells skeletal smooth and cardiac muscle tissue is excitable the second one we're going to talk about now is the nervous system neurons neurons are excitable cells they have all these ion channels that allow electrolytes or ions to move through their membrane and change their voltage how and why we're about to understand I'm gonna try to give you the best understanding that I can of them in a simpler format as possible you can read the textbook and get into the more complex understanding of this stuff get into more complex details but just follow along now in order to understand how neurons function I'm gonna draw a generic cell here I'm going to talk about ions and ion flow and different types of channels first and then we'll talk about neurons in specific so if I were to take a large cell here and just draw it out okay typical cell lipid bilayer I'm not going to draw both layers of the lipid membrane but you get the idea back in the 40s some scientists realized that you know because of these voltages what's causing it what's causing the voltage to run through these neurons and a lot of the studies were done in the giant squid axon but anyway what they realized was it's it's because of these compounds called electrolytes electrolytes are things that are electrolytic they carry a charge an electrical charge so we're talking really essentially about the ions in our body and one of the most abundant ions that they could measure they were measuring the concentration of sodium ions sodium in Latin is natrium so na as the sodium symbol and that's an ionized sodium atom so we talked about atoms and ions and how they occur early in the semester the brackets if you're not aware in chemistry mean the concentration of whatever's inside there turns out that sodium ions have a much higher concentration outside the cell then inside of the cell and this sets us up for the laws of diffusion as you know in the fusion if I'm measuring outside the cell and inside and I'm looking at sodium ion concentration I mean it makes sense for just looking at the slope that sodium is going to move from outside the inside the cell if the membrane is permeable well it turns out that many of our cells not just excitable cells but many cells have these little channels that penetrate the cell membrane these are proteins that cross the membrane a number of times and form these little tube like channels and the electrochemical properties of these channels are such that some of them only allow specific ions to flow and since this channel is considered what we call a leak or passive channel so when we talk about leaky channels or a leak channel they are passing what that means is they don't have to open and close or do anything to allow the ions to flow across so naturally by the laws of diffusion sodium ions would flow from outside to inside the cell from air high to low concentration simple law of diffusion now someone also measured the concentration or the same group of guys measured the concentration of potassium ions and it turns out the potassium ion concentration is much higher outside of a site inside the cell than it is outside so if I set up the concentration for potassium ions and I were to look at potassium this way potassium ion concentration is much higher inside the cell than outside so potassium wants to leap from inside the cell to outside so all I need is a little leaky potassium channel and potassium ions would leak out of the cell and they carry with them these charges making them electrolytes now if I allow this to go unchecked if I don't stop this from happening essentially what's going to happen is the concentration of sodium here which is higher than here as sodium leaks in this concentration will go down and this one will go up and then will reach an equilibrium and then there's nowhere for the ions to flow same would be true from potassium we do not want to be at equilibrium if you're at equilibrium your room temperature you're dead you want to be at a homeostasis or steady state which requires the input of energy to maintain this imbalance and as you should have learned at some point and if you haven't we're going to cover this our cells have in them an ion pump called the sodium potassium exchange pump or sodium potassium ion pump some people just call it the sodium potassium pump or it's also called the sodium potassium ATPase so let me just write this out ATP as you know is adenosine triphosphate that's what we break to make energy or utilize energy and anytime we have ASE at the end of the word it means it's an enzyme so the sodium potassium ATPase or sodium potassium ion exchange pump it's going to be a protein that crosses the cell membrane and it turns out that it has certain docking sites certain numbers of islands to mind so when we look at this it turns out that [Music] the way the protein is set up is that it can bind to three interestingly your sodium ions I apologize for this board knocking I'm gonna try to get used to holding it but I got a bigger board it just doesn't sit against the wall see three sodium ions bind on the inside two potassium ions bind on the outside and when they bind as the protein changes shape that allows a molecule of ATP to be broken down so our cell the mitochondria if they have adequate oxygen and glucose or pumping out ATP like crazy when these are bound this molecule will break down ATP and ADP plus phosphate breaking that phosphate bond off makes this into a TPAs and enzyme that breaks down ATP that releases the energy in that bond for the protein that's changed shape and when it changes shape it boots out the three intracellular sodium ions that leaked in and it will kick in to extracellular potassium ions go into the cell and all of this stuff is happening in such a pace and there's just the right number of sodium potassium pumps and the sodium ion channels and potassium ion channels that it keeps the cells normally at this imbalance okay there are other ions and other ion pumps involved there's chloride and calcium but these are the major ones that play a role in the action potential this can all be worked out of it's called the Nernst equation into the Hodgkin goldman katz equation we're not going to give in to that that's if you were in a higher-level neurobiology class but nonetheless when the scientists measured these concentrations it gave them the ability to do some math and predict what the voltage of the inside of the cell should be compared to the outside and rather than give you exact numbers I'm just going to get something across because and many people will argue that when we measure the voltage across this cell it turns out that if I took let me draw a little scenario here if I had an oscilloscope which I could be reading something on here and I took an electrical probe like a metal needle and another metal needle and I set them across here across the cell membrane that could be measuring the voltage across the cell membrane almost like a voltmeter where you check the car battery and then this voltage would tell me what the voltage is this this oscilloscope or voltmeter could tell me what the voltage is across the cell memory and a lot of people will tell you because we're dealing with only positively charged ions that the inside of the cell is negative because of all the negatively charged proteins and the negatively charged DNA and bla bla bla but there's actually some mathematical equations that were worked out by these guys actually got copies of the original papers when I was a graduate student studying the neurobiology and it turns out that it's due to the equilibrium constants and the equilibrium of these things that we can figure out or predict what the voltage in here should be when they did the math it turns out that the inside of the cells should be 68 or we just say 70 millivolts lower than the outside so let me just show you something this is not really testable but let's say let's say the inside of the cell actually measured 80 millivolts and the outside of the cell measured 150 millivolts on this particular cell well the math gets kind of funny when we're dealing with these numbers and they said we maybe we should zero something out and since they're same all the cells of the body would have the same reference which is the extracellular fluid let's make the extracellular fluid zero millivolts that will be our baseline and when I measure this particular neuron I also have to do the same thing to the outside that I did to the inside and it should be 70 millivolts lower than whatever the outside is that's not exactly what they did but it kind of works out that way and it's really based on the ion concentration when you do the equations and you do the mathematics I've done it a lot of times turns out they predicted the inside of the cell should be minus 68 millivolts and lo and behold it read exactly what they predicted so now so we know that when we measure the voltage difference based on the imbalance of ions that the inside of the cell we just say is minus 70 millivolts so now there is such a thing in addition to leaky channels and by the way we call this I'm going to put the letters R MP here which stands for resting membrane potential at rest the potential difference across the membrane meaning and when I say at rest that means the neurons not conducting action potentials while the neurons at rest the potential difference of the electrical voltage across the membrane is about negative 70 millivolts so minus 70 okay now what if I introduced a new kind of channel we call these gated ion channels because they actually have doorways or gates think of a move like a trashcan when you step on the trashcan the lid opens okay you can't put anything in the trashcan or getting anything through the tube unless you open it so let's say I have an gated ion channel here that has a lid on it okay and this one's electrochemical properties are such that only sodium ions can pass through it nothing else because of the in equal distribution of sodium potassium inside and outside the cell if I do open this channel then sodium starts to leak into the cell and as long as the channel is open sodium ions due to the laws of diffusion will continue to move through here bringing positive charge well what's that going to do to my resting membrane potential and when I do open sodium channels I should see the membrane potential go up as a matter of fact we start to draw this as what we an electrical diagram which is called a it's the action potential diagram I was drawing a blank there for a second forgive me so I can be measuring the voltage across this thing and if this is let's say we put here zero millivolts up here we put plus 30 millivolts there's a reason we're using these voltages you'll understand eventually so if I do that then double that would be minus 60 millivolts will go down a little bit more to minus 70 millivolts which minus 70 hours our resting membrane potential and then we could go down further say all the way down to minus 90 millivolts and there's a reason I'm using these numbers you'll see shortly let me take this thing off I'm not putting my markers on it so if I did nothing to the cell it would be sitting here running at minus 70 millivolts the very instant I don't care about the time frame we're not going to do those numbers right now the very instant that I opened one of these gated sodium channels because sodium rushes into the cell the cell would start drifting to a more positive voltage if I had even more positive ions to it then it would become even more positive the minute I closed the channel eventually given enough time the sodium potassium pump will eventually catch up by pumping out all this sodium and restore us back to rest so anytime I activate or open a gated sodium channel I'm just gonna put sodium plus and a little G therefore a gated sodium channel okay if I open a gated sodium ion channel I'm always going to get the cell to go from a already polarized potential we're not sitting at neutral zero we're polarized towards the negative pole like a negative and a positive pole on a battery and since the cell is polarized to minus 70 if I start to move closer to zero I'm depolarizing the cell so any movement in the positive direction going toward zero is depolarizing my already neuron and sometimes when we depolarize sometimes we use the same thing we say that we excite the cell and I'll tell you why you're seeing just a little bit now if I don't hit this voltage - 60 millivolts that's a big deal we'll talk about that in a moment so every time I flash up in the sodium ion channel the longer I flash it open open the more I will see the cell move in a positive direction now let's say I have a gated potassium channel it's specific for potassium ions and since we know potassium is in a much higher concentration inside the cell than outside the second I open this potassium ion channel potassium ions start to diffuse out of the cell while taking potassium ions out of the cell is taking positive away from an already negative situation so let's say at this point in time I open a potassium gated channel I activate it or open it when those channels are activated or open we see that the cell starts to become more negatively charged inside and the longer I hold it open the more positive ion is lost the more negative it becomes the instant that I close this channel and I quit losing positive ions then the sodium potassium pumps which are all over the cell will eventually restore us that to rest okay so now I can alter the resting membrane potential by opening and closing gated ion channels so this is a simple concept but it's going to be a big one that comes to play in just a little bit okay so if you're following along on page 65 it's to talks about all this it talks about the resting membrane potential how it's established by sodium potassium ions the sodium potassium pump and it talks about excited shell cells having gated ion channels channels it can open and close now there are three different types of gated channels that we're going to discuss they're listed on the bottom of page 65 of my note said there are chemically gated channels chemically gated channels can open and close due to the presence of specific chemicals those chemicals can be neurotransmitters like acetylcholine binding to acetylcholine receptors which by the way are attached to sodium ion channels which why is why the muscle cell depolarizes or had a voltage spread on the sarcolemma so chemically gated channels open and closed due to the presence of specific chemicals i've talked about this before and some of my lectures i can't remember which one so i'll just mention it again when proteins are synthesized proteins have a long chain of amino acids stuck together in all these chemical bonds it turns out that some of these amino acids have little side groups some sodium's and I'm sorry some carbons and hydrogen's and oxygens and in some of those side groups if I put these two together one will give off hydrogen the other will give off a hydroxyl and OAH group in dehydrate and form a chemical bond so if I put those two amino acids close enough together the protein will fold over on itself there are natural chemical reactions what that does is it might bring two other amino acids into close proximity and so then the protein continues to fold and over time the protein can fold up into a specific three-dimensional shape with all these little chemical bonds inside of you when proteins fold up and take on their natural form we say this is the nature protein or its natural shape now because the chemical electrochemical properties of this there are certain other molecules that who's either electrical charge or electrochemical properties might bind to some of these amino acids for example let's say that these two right here that form this little chemical bond here and these two right here are somewhere in this area and I have another molecule that can bind to this region these little atoms or ions here match up to atoms or ions there but in order for these two binds some of them might have to break one of their chemical bonds and change the shape of the protein and so when they do when this bond happens this protein which is shaped something like this might have another piece that sticks out because of a loss of a chemical bond here when I remove this it will go back to its original shape so the point of this is proteins have a three-dimensional shape they're bound to certain molecules or certain substances if I make them bind to something else they might change their shape for example you might be standing here like this if someone comes by say an old friend or a family member and you go to give them a hug you might change your shape to interact with them in order to do so instead of standing still you might have to step forward with one of your legs so binding in one part of your body interacting with someone in one part might cause a change in the positioning of your legs or something like that the best example I can give is if I told you guys stand here like this and don't move your arms the entire class period and I'll give everybody a hundred on the test and then I toss things at you some of the things you you don't have a high affinity for you don't want to bind to them I toss you a tennis ball or a baseball or you know wadded up piece of paper an eraser you can stand it I want that a if I threw you a live baby you would change your body position and bind to that baby well that's kind of what happens when a chemical binds to a chemically gated ion channel it'll cause it to open we call this a lock-in key hypothesis because sort of the three-dimensional shape of a specific key will fit in the receptor which would be the the slot for the key the lock itself and then when when we when they bind that can open a door and that's how chemically gated ion channels work some chemical a neurotransmitter a pharmaceutical agent an illegal drug binds to a receptor in the membrane of the cell when I mind it here that can cause the channel to open in that sodium rushing chemically gated ion channels we also have voltage-gated ion channels so if I ask you to stand like this for the whole class and I shocked you with the mild shock you might not move but if I stuck a really high voltage taser on you you might go well that's gonna cause you to change shape so some channels both sodium potassium channels and other ion channels calcium channels can be shocked into opening voltage-gated channels we shocked them they open ions flow through when the voltage changes and disappears they close that's how the calcium channels work in the synaptic knob when the action potential arrives they open when the action potential disappears they close that's calcium into the synaptic knob for neurotransmitter release and like we saw on the motor endplate neuromuscular Junction and then we have what are called mechanically gated ion channels mechanically gated ion channels open and closed do the physical distortions in the cell membrane I think of it like this okay so this is an ion channel a protein and this is just so membrane right here here sorry giving the camera if something presses hard enough on one of my arms it might pull my hands apart when that press is gone then it goes back it's a physical or mechanical distortion causing the ion channels to open these are almost like those little error of nozzles on kids floaties in order to blow them up or let the air out you have to pinch the NAS that would be a mechanically gated channel so we have three different gated channels that we can open and close to alter resting membrane potential to either depolarize it or excite it or sense and I didn't do this so since let me erase my little protein binding here since the potassium channels when they open and potassium exits the cell we lose positive charge and become more negative we're already polarized if I become more polarized than normal the cell is said to hyper polarize and we'll call that I'm gonna say it inhibits the cell one excites the other inhibits well how and why we use this terminology exciting and inhibiting will become apparent to you in the next video so this video was to explain page 65 which is just ion channels and the sodium potassium pump and the fact that we have leaky channels and we're leaking sodium in and pumping it out and making potassium out and pumping it back in at a rate of three sodium's from inside the cell get pumped out we pump three intracellular sodium's out of the cell and two extracellular potassium back into the cell the shape of the protein is such that it works that way and every time it does so it breaks down a molecule of ATP so just to remain at rest or requires energy that's our resting state or homeostasis we can alter that resting state only in excitable cells excitable cells have gated sodium and potassium channels because of the concentration gradients every time I open a sodium channel sodium rushes in the cell depolarizes or moves closer to zero every time I open potassium channels because of the concentration gradients potassium exits the cell and the cell will hyperpolarize or become more negative now the numbers for different cells may change slightly skeletal muscle cells and cardiac muscle cells and different neurons use slightly different numbers but essentially the concept is always identical once you understand one action potential you understand them all the numbers may change some of the ions involved might change a little bit like when we do the cardio side action potential in part two but else in essentially it's all based on this principle okay so gated channels are only found in excitable cells almost all of the cells of the human body have these leaky channels and sodium potassium pumps and they're constantly battling this but most of our cells don't have gated ion channels only neurons and muscle cells which allows us to have action potentials for them so understanding all of that sets us up for the next video which is going to we're going to see how action potentials they spread down neurons and the same concept would be true for skeletal muscle and muscle cells how does an action potential spread down them same concepts same theories same philosophy anyway so I hope this was helpful for understanding ion movement in the cell and understanding resting membrane potential and how we can mess with it with gated channels I hope you learned something I hope you had as much fun as I did so I'm gonna stop here and we'll do lecture number four and the nervous system where we actually do an action potential in a neuron thanks for watching see you on the flipside