is this the weather you all been waiting for yeah it's pretty nice really nice weather nice and 68 yeah 68's the magic number i feel like it's probably the magic number plus or minus it's a day where you could be comfortable in the shade or the sun right okay a few announcements uh so what's happening next week what's the schedule next week online for what day monday's lecture but we're going to have activities in class okay so activities in class next Monday and activities in class next Wednesday review session style for the exam that happens a week from Monday make sense i'll put up the study guide this week uh we are moving the Sunday session to Saturday because Sunday is Easter what time on Saturday uh noon noon to 1 what room bio 256 bio 256 noon to one on Saturday it'll be on Zoom and it'll be recorded as well okay but I don't want to interfere with your ham lunch if that's what's going to happen okay um we have a quiz due next week but maybe you get it done this week that's quiz seven that's due i worry if I'm not here next week because I'm traveling and I don't remind you you'll forget so maybe just get it done by this Friday does that sound like a good deal okay so this is the second of three lectures on neurohysiology so the third lecture is going to be on YouTube posted from last semester uh I did notice that the the lecture from Monday for some reason is taking a while to get cleared by YouTube maybe I was overly crass in my video and I got censored on something i don't know i can't remember do you guys remember did I say something okay i don't know but it's not loading i've tried it twice and it's like I don't know we'll see what happens we may have to be relegated to the fall lecture but I thought Monday went pretty well i don't know what do you guys think i thought it went so I hope it gets loaded okay let's let's chat a little bit about um some really important topics why are animals in the ocean so healthy huh they're hydrated i like that and they also get in addition to that their daily dose of vitamin C where do cats wait to pay their bills where do cats wait to pay their bills any cat lovers come on cat people raise your hand be proud in the feline oh okay all right this one this one takes me back this one was actually written by my daughter my youngest my baby who's turning 16 um like in a week and a half and she wrote this when she was five okay long time ago what is Darth Vader's favorite dessert i thought that was pretty clever she's a clever one all right shout out to you Ree all right with that let's talk about uh action potentials this is going to be I think great material for you to review for the exam and our TAs and our SI are very well prepared to to navigate this with you you can rewatch the lecture if you need to kind of refresh the details we're going to go kind of straight into you know the nitty-gritty after I sort of make this reference so I've told you that if you have a motif in biology you tend to see it again and so if you focus on the tops of these aspens can you see how the spacing is and to me it reminds me of dendrites on neurons and so you're going to see a lot of these you know the round wheel the round steering wheel right we see the organization of bone muscle the organization of nerve fibers we see architectural similarities in biological species and a lot of this is because it works so here you've got kind of a plant connection architecturally to neurons so I mean if you're next time you're on the lift and you're just staring talking to the person next to you maybe could bring up like don't those look like neurons to you like dendrites strike up a conversation see where it goes okay homework i want you to do this now though i want you to draw a typical sematic cell and I want you to demonstrate what's happening at resting membrane potential where sodium potassium and chloride are high and where they're low if you know the Millie equivalent numbers bonus well not really bonus but okay i'll give you a thumbs up might be bonus later so stick around but I I want to make sure that you guys understand how this sketches out so take a second to draw this it's not a bad activity to find some white space on your test packet and just draw it out and then refer to it when a question comes up about some of these topics right it's like a pro tip on studying see some pens still up so we'll kind of hold for a little bit if you're done drawing think about when a sodium gate opens which direction is sodium going to go think about when a potassium gate opens which direction is a potassium gate going to go or potassium ion going to go okay so it looks something like this see some nods it's really all I was looking for was what we talked about on Monday it was kind of review for Monday right so what is ECF in the upper left what does that mean extracellular fluid and what is ICF in the lower left mean intracellular fluid what is the yellow smear across the middle phospholipid billayer also known as what in a nerve oh axolma nice lip reading we have a a sodium channel here i didn't ask for this but we have a sodium channel we have a potassium channel but I did ask for where is sodium high and where is it low so you tell me where is sodium high outside the cell where is sodium low inside the cell so when a voltage gated sodium channel is triggered to open which direction does sodium go into the cell via what mechanism simple diffusion thank you okay potassium ion is high or low outside the cell low and it's high or low inside the cell so when a voltage gated potassium channel opens or a leak channel remains open which direction does potassium flow via what mechanism out of the cell simple diffusion again chloride ion know that it's high outside and it's low inside it kind of likes to follow sodium because it makes salt sodium chloride that's how you remember that if you remember sodium you remember that chloride likes to be around it so then you know the same relative distribution that make sense what are these green structures ann ions they're charged how negatively if they were a cation they'd be charged positively but an annion is a negative charge they're too large they can't escape the cell they help they help to establish this slight negative charge inside the cell rna DNA these proteins contribute to a negative charge but what helps to really maintain the negative charge especially at this interface right here just beneath the surface sodium potassium pump or the sodium potassium ATPAS called an ATP ace because the ATPA the enzyme anything that ends in ACE is typically an enzyme that cleaves the phosphate groups off of adenosine that has three phosphates that's why we call it adenosine triphosphate every time it cleaves a phosphate it liberates energy so you saw in the video on Monday when we remove the first phosphates we actually pump three sodiums out and when we remove the last phosphate we pump two potassiums in so the sodium potassium ATPAS or the sodium potassium pump is running when does it run when is it on all the time it's always running to maintain this differential this potential so I want you to talk to your neighbor about person A you identify who's person A and you identify who's person B how do ions move in and out of the cell i already talked about voltage gates i want you to explain lian gates person A and then person B I want you to talk about channels and mechanical gates and maybe give some examples goodbye all right let's hear from person A i talked about a voltage gated sodium channel can anybody in person A group give us another example of a voltage gated channel that we've actually already learned about in another unit it is the calcium one well done i'm impressed do you guys remember the calcium voltage gate in muscle physiology when it when the signal comes down the T- tubule and it triggers a voltage gated calcium channel to dump calcium into the cytoplasm of the muscle cell to bind to dropponin to open up the binding site for the measin head you remember all that yeah so we've already seen the voltage gate once before and we just talked about a sodium voltage gate okay well done that's really impressive ligan gates person A what's an example of a lian gate something binds and it opens a channel to allow ions to flow we've also already studied this one before too here's a hint same system as the one we just talked about acetylcholine wow you guys are really on it today i love it yeah acetylcholine remember acetylcholine crosses the neuromuscular junction on the presinaptic side binds to its receptor opens up a channel allows sodium to flow in that's another example of a lian gate all right person B you got some high bar to achieve here we have 100% on person person's A people's A example of a channel i've mentioned this before in lecture Monday as well as today already what's an example of a channel moving ions the channel open and close or is the channel pretty much always open it's always open it's the potassium leak channel man you guys are sharp sharp sharp mechanical gate let's go for 100% what's an example of a mechanical gate this one might be a little challenging this is the reason I still have a job so thank you if you don't get it what's an example of a mechanical gate so we haven't really talked about this yet i mean if you read ahead you might you might have caught it but this is where you actually mechanically touch or stimulate with pressure or force right so for example if you go back to the integimement or the skin we had a lot of receptors in the dermis like misner's core pusles rafinian core pusles touch receptors that when you put pressure on them mechanically it opens the gate and sodium flows and that sends the signal via the sensory receptor from the periphery to the central nervous system and you say "Ow that's a sharp corner." Okay that's mechanical gate so all of these different types of gates are regulating the flow of ions so the key that makes this happen is way the way that ions move does that make sense you have four different ways that you can make ions move but the secret separate the ions create a potential open up something and allow ions to flow and then as those ions flow you create a disruption or a difference a potential in the electric charge right in that area does that kind of make sense i'm going to show you pictures but conceptually I need you guys to kind of get your head around what an action potential is and how it actually works that's the goal of today okay so answer a couple of questions here which is in higher concentration inside of a typical sematic cell that just means body cell any cell neuron muscle they're all slightly what negative so what's higher in concentration inside what's higher inside potassium thank you okay very good what causes a cell to be negative what causes it not saying what maintains what causes it to be slightly negative does chloride ion have anything really to do with it no it doesn't just kind of follow sodium it's like a puppy dog okay copycat presence of nucleic acids inside the cell yep presence of proteins inside the cell they can't leave i would agree to read the whole question because it is e two of these nicely done all right let's look at this animation unstimulated neurons maintain a constant electrical difference or potential across their cell membranes this potential called resting potential is always negative inside the cell and ranges from -40 to9 ms if a neuron is stimulated the negative potential inside the neuron can be made either more or less negative depending on the stimulus if potential is made sufficiently less negative it reaches a level called threshold and an action potential is triggered during the action potential the neuron suddenly becomes 20 to 50 volts positive inside action potentials last a few milliseconds before the cell restores its negative resting potential okay just wanted to see if you could visualize it briefly before we start talking about it in more detail so the resting membrane potential of a cell is due mainly to what what's another way of saying this so this would be a great example of a test question that you don't understand like what are you getting at so another way to look at this is okay I don't see the answer on the sheet or the options it's what I would select right it's due to what what would you want to say how would you want to answer this if you could just answer a fill-in- thelank resting membrane potential is due to what it's created by or it's maintained by which which option do you want to go with okay you think it's B that is the correct answer here but I'm trying to navigate you through so some of you are thinking like I don't see the right answer on here because I would have selected like negatively char annions or nucleic acids or proteins establish it and it's maintain maintained by the sodium potassium pump so another way of reading this question is what's happening during resting membrane potential the only thing that's happening during rest is open potassium leak channels so that's why you go with B does that make sense so sometimes if you're reading the question you're like I'm not really certain what he's getting at because that's not what I would have answered then think about what's true in that condition and see if you can eliminate stuff okay um we're going to do this now i'm going to assign another homework but I'm going to have you do this now so I want you to see and and pay attention to these different ions so we have potassium ion K+ we have sodium ion Na+ and we have chloride ion and these are the miller equivalents of each that were on that sheet the earlier image so potassium is high intracellular fluid concentration that's what this is saying so these little brackets in this notation mean concentration sodium is low inside the cell potassium is high inside the cell chloride ion is also low inside the cell and in the extracellular fluid or the outside of the cell we have just the opposite we've got potassium ion being low sodium ion being high and so chloride ion being high so now I want you to talk about the forces there's two different forces that we can fill in and the answers that you're going to put here are going to be either into the cell or out of the cell that's what's going to go in the box so let me ask this question is the diffusional force in other words the concentration gradient for sodium ion is it into or out of the cell based upon this data it's what into why is it into the cell because it's high outside and it's low inside so the diffusional force is into okay what about the diffusional or concentration force of potassium into or out of out of so you write out of right here now let's look at the electrical force that was the easy one let's look at the electrical force but it's not that complicated so sodium ion is positively charged and the inside of the cell at rest is what slightly what negative opposites do what attract so which direction is the electrical force for sodium when you open a channel into or out of into so you have into and you have into potassium you tell me the electrical force it's into right into So now it should look something like this correct so if I open a sodium gate at rest do I have more forces driving sodium into the cell than I do potassium doing anything yes why i have two forces going into and potassium kind of has a conflict if you will so when a sodium channel opens sodium ions are going to rush into the cell very quickly because it has two forces that are working collectively and the sodium rushes very fast potassium is going to leave the cell but it leaves the cell more slowly because it actually has a competitive force the electrical force that it's kind of working against so sodium movement is quick potassium movement is slower does that make sense based upon these data that we have right here so that's a very important tenant to think about when you're talking about an action potential and I'll explain here as as we move on in the lecture but these action potentials what is an action potential who can define it for me any takers just give it a shot yeah a rapid electrical signal around an axon i like that i think the only thing I would add to that is that signal has reached threshold to propagate that electrical signal along the axon because that's the big difference between an action potential and a graded potential or a local potential a local graded potential doesn't reach threshold so for example these are excitatory postsaptic potentials epsps you're like well that's a lot of words excitatory stimulates a signal it's on the post synaptic side on the other side of the syninnapse and it's creating a potential or an electrical difference if you get a stimulus every time there's an arrow and you see a little blip you stack these these are all local graded potentials but once they hit minus 55 it hits threshold and then it turns into an action potential so on this graph all of these EPSPs are called local graded potentials and this giant one up here is called an action potential the other thing that I should note because one of your classmates asked this question after lecture on Monday so in this class we're saying that minus70 is resting membrane potential thresholds at minus 55 and you get to about positive 30 positive 35 there's a range like in the video it talked about that range did you see that in the video in the opening part of that video so depending upon if it's a muscle like like muscle cells are more like minus 95 nerves are like minus70 so sematic cells have a little variety but for the purposes of our class we're going to say in nerve physiology RMP is minus70 just for simplicity does that make sense i just don't want you to move on another class and be like oh wow I I thought the number was minus70 and now they're these two professors disagree about this number okay there's a there's a range the action potential really only occurs where there's a high concentration of voltage regulated gates voltage regulated gates this happens in the axon hillic kind of in that funnel which we refer to as the trigger zone and stacking local potentials or graded potentials can lead to an action potential that all make sense so the different parts of the action potential we're going to park on this slide for a little bit and this would be a really important slide to study for your exam a week from Monday we have seven different segments labeled on a traditional action potential and sort of the difference between this picture and this picture is this one is highlighting these local potentials that lead up to threshold this one's just showing the local potential all by itself reaches threshold that's just the big difference okay if this prior image this local potential was all that fired and none of these extra ones fired it never would have reached threshold this one was just a big enough signal that it reached threshold all by itself so we will show this picture in the next couple of slides just for simplicity and we're going to talk about physiologically everything that's happening at each one of these points okay they're conveniently numbered for you so at number one we have sodium ions that arrive at the axon hillic depolarize the membrane at that point number two the depolarization that just means becomes more positive from minus70 it approaches -55 do you understand how that's becoming more positive it's getting closer to zero -70 is further away from zero here's zero - 55 is closer to zero it's less negative so you depolarize it you reach threshold at step two typically around minus 55 millolts at this point that triggers voltage regulated sodium i call them fast gates they open and sodium saunters into the cell meanders into the cell or does it rapidly infuse into the cell it rapidly infuses into the cell and that's why this happens so fast you see the spike that's step three the sodium voltage regulated fast gates are open now also what happens is our slow voltage gated potassium uh gates open in step three but they don't take as much time or they take more time they don't go as quickly but at 4 is when the propagation of the signal stops and the sodium voltage gates close at four the slow potassium gates are still opening they remain open in five in five the sodium gates are totally closed and the potassium gates are fully open and now you're repolarizing the membrane making it more negative again because which direction is potassium going out of the cell taking a positive charge with it making the inside of the cell more what negative so this makes it more negative more negative we call this side repolarization we call this side depolarization in step five the sodium voltage fast gates are closed the potassium voltage gated slow gates are open they're also those gates are slow to close so because they're slow to close and they don't shut quickly like the sodium gates do you get this overshoot in step six more potassium leaves slightly more than what's needed to stabilize the minus70 resting membrane potential so you overshoot it by like minus75 or minus 80 and then in step seven how do you reestablish the resting membrane potential that you've you've lost a little too much potassium than you should have what mechanism reestablishes the right balance of ions to reset this the resting membrane potential what is it you know this answer it's not diffusion something that's running all the time the sodium potassium pump is what is responsible for number seven of reestablishing and resorting three sodiums out two potassiums in you with me i know that's a lot of information do you want me to walk through it one more time yes please okay we just go right rewind the video step number one I'm gonna ask for some audience participation somebody walk me through what's happening at step number one you can use the slide you can read it that's fine but explain to us what's happening step number one any takers sodium ions arrive at the trigger zone of the axon hillic and depolarize the membrane at number one is this a action potential local potential or graded potential or two of these two of these which ones local or graded that's right okay great what's happening at two what's significant about step two it's threshold what's the numerical value that you've reached minus 55 have you deolarized the membrane or have you repolarized it you've depolarized you've made it less negative what's happening in step three sodium gates open are they fast or slow they're very fast allow sodium to do what moves which direction into the cell down which forces simple diffusion so there's a concentration force and there's a electrical force right so it goes very quickly in step three what else in the background happens in step three what else opens the slow potassium gates start opening what's significant about four it's like an abrupt boop what what closes at four the the fast gated sodium gates close they shut just like that and and the membrane potential does this immediate 180 because in step five what's open not the fast sodium gates but the slow potassium gates and which direction is potassium flowing out down its what gradient concentration gradient because it's high inside the cell and it's low outside the cell if potassium flows out in five is it repolarizing or depolarizing the membrane because it's a positive charged ion taking a positive charge out of the cell leaving behind a negative balance you with me why does it become more negative than we need it to be you told me that minus70 was the resting membrane potential why is it going beyond that i don't like that why is it doing that is the potassium channels are slow to close potassium potassium gates the the voltage the slow voltage gates of potassium are slow to close right the leak channel is always open so we we're not talking about that one right now and so that means too much potassium goes which direction out of the cell taking a positive charge out of the cell leaving behind a negative balance and then in seven what is always on and helps to reestablish resting membrane potential reset the ions sodium potassium ATPAS okay we did that twice the second time I feel like you got it you needed a third time we have the video right you want it a fourth time we've got SI sessions fifth time we have TA sections sixth time Saturday before the exam on Monday seven eight ninth time you can do it next week on Monday and Wednesday right here there's a lot of opportunity for you to get this down is that you with me really important to know okay so let's talk now we're going to use um some of this information as we kind of move forward now that we've set that the characteristics of an action potential versus the characteristics of a local or a graded potential because they are uniquely different and an action potential is an all or nothing response once you hit threshold you can't take it back it's it's trains left okay fire the neuron you can't bring it back but right up until you reach threshold you could so an action potential is all or nothing it is nondremental that means it doesn't fade it's not like in this graph right about here it's like oh never mind like like if it hits minus 55 it fires and you have a signal going so it doesn't dissipate it's also not reversible you can't back it up now there's a couple of important pieces about this after an action potential we have what we refer to as a refractory period where the neuron loses its excitability and won't fire again and this is a mechanism so that you propagate the signal forward and you don't accidentally propagate the signal in the backwards direction so this ensures that the movement of ions that's propagating you know there's voltage gated sodium channels the other direction just like there are forward direction but if you hyperpolarize the membrane behind the signal then the path of least resistance to move ions and trigger a signal is in the forward direction so we have an absolute refractory period where when it's firing you can't send another signal you don't want to cross the signals you want signal fidelity or signal purity is the way that that would translate so during the firing of an action potential we have that is called an absolute refractory period you will not fire another signal after you've repolarized the membrane here in yellow you've hyperpolarized it you have a relative refractory period so it it's less excitable a signal of great strength could actually fire another signal in the in the nerve but this relative period kind of prevents it from moving in the backward direction so absolute versus relative two stages so this is a table that I want you to do at home and then on Monday the SI's and the TAS are going to go over the answers to this table you're just comparing contrasting an action potential versus a graded or a local potential on the far right column so you're going to answer questions like is it an all or nothing um event so it's going to be like yes or no uh is it decremental over time and space yes or no can it be inhibitory yes or no is it reversible you you you understand the concept right so that's Monday's in-class activity we'll share those answers okay question so far okay we're going to get more into the mechanisms of how the signal propagates and how it travels and to do this I'm going to show you these three different pictures on the far right side of the slide where we're getting this image from is this little box this square up top of a what type of neuron structurally a bipolar neuron exactly bipolar neuron so these are the dendrites here's the cell body here is the axon the signal is moving from left to right we have a a square here and we're highlighting this segment here's the trigger zone this little like funnel but we're going to just take a snapshot somewhere along the axon of what's happening and if you're seeing a green area you can see inside the cell it's slightly negative here inside the cell it's slightly negative all the green inside the cell inside the neuron it's slightly negative you can see as the action potential which is colorcoded in red is happening you're moving this action potential from this position from left to right and right behind it is this relative refractory period so it's going to want to move in the path of least resistance which is in the forward progression direction so does that kind of help visualize the purpose of the relative refractory period so we get our signals moving in the right direction so this signal that's propagated in an action potential can go through kind of two different processes we can either do this what we call continuous conduction which is what I'm showing you that signal is continuously conducting down the length of the nerve now if I cover portions of it in myelin I complicate the issue because now where the myelin sits there aren't voltage gated channels the myelin is covering them you can't move ions so what happens is the signal moves completely around the myelin and goes to the next bare spot it's like a shortcut it's like a video game hack so saltatory conduction only happens with mileelinated axons and it speeds up the signal because it literally hops from one bare spot node of revier to one bare spot it doesn't have to do the continuous conduction all along the path there's two main things and I'm going to show you a video here in a second after this concept that influence the conduction speed number one is mileelination so if the neuron is mileelinated is it faster or slower than a non-minated neuron faster okay you guys got that down know that remember that the other thing is diameter if it's a larger diameter versus a smaller diameter which one moves the signal faster larger think of um uh a milkshake do you want a large straw or a skinny straw more milkshake can move through a large straw in any given unit of time more signal can move through a larger diameter neuron same is true in electrical wiring okay you have a really nice stereo sound system in your car or at home you're putting out significant amounts of power you buy larger in fact there's a whole company that's designated to monster cables right big diameter wiring to get better quality signal faster with less heat so larger diameter diameter mileelinated is the fastest mileelinated is the fastest combination so on the exam if I had a combination so on the exam if I had a question that said which of the question that said which of the following sends the signal the fastest following sends the signal the fastest a a a a mileinated one micron diameter neuron b mileinated one micron diameter neuron b an unmilinated 1 micron neuron c a an unmilinated 1 micron neuron c a mileinated 10 micron neuron so larger mileinated 10 micron neuron d an unminelinated 10 micron neuron which one is it c why milinated and it's 10 microns which is larger than one okay you guys got it so we can graph this something like this we've got our fiber diameter 05 10 15 20 in microns and this is out of a a French journal so fibre but a conduction velocity increasing from zero to 120 meters per second and you can appreciate mileelinated fibers have a completely different curve than unmilinated fibers but if you have a 20 micron unmilinated fiber it's actually faster than a one micron unmilonated fiber but that difference is exaggerated when you add mileelin does that make sense okay all right i want to show you this video of continuous unmilinated versus saltatory mileinated nerve fiber during the milination of neurons action potentials may only occur at the nodes of rounder myin is made up of insulating cells which means depolarization cannot occur in mileinated regions between these cells however there are gas known as nodes of which are unmalinated cannot occur at the cells making up the shape the wave of depolarization can only occur at the nodes around you thus action potentials appear to jump from node to node when traveling down an axon and this phenomenon is known as salary conduction and it serves as a means of increasing the rate of propagation of an action potential not only does self conduction increase the speed of impulse transmission by causing the depolarization process to jump from one node to the next it also preserves energy for the axon as depolarization only occurs at the nodes and not along the whole length of the nerve fiber as in unmilinated fibers this causes up to 100 times less movement of ions that would otherwise be necessary therefore conserving the energy required to reestablish the sodium and potassium concentration differences across the membranes following a series of action potentials being propagated along the fiber okay does that help kind of make it relatively clear on on what we're talking about okay so this is another video I want to show about the involvement of Schwan cell and and so I'm going to hand out um an assignment uh on multiple sclerosis uh at the end of class a bonus assignment and it's extremely relevant to what we're talking about here and and and multiple sclerosis that we'll talk about in a second is an immune deficiency disease where you attack your own myelin and destroy it so you lose this saltatory conduction and you replace it with continuous conduction so let's take a look at the role of this gal cell right the Schwan cell nervous system and the propagation of the action potential along the multimedia presentation will be most helpful if you already have a good understanding of cellcess forms a protective cover do you see how it wraps cells start to develop in the embryo and continue to increase the wrapping around the axon through childhood this development increases the thickness of the wrapping which peaks in adolescence this is why teenagers have such quick responses the schwan cell contains the typical cell organ however notice as the cell surrounds the axon that the nucleus and other organels are squeezed to the outside of the cell this outer wrapping of the schwan cell is called the neurolma we learned about that the inner lining is made up of layers upon layers of cell membrane this inner wpping is called the myelin sheet you will recall that the cell membrane called the fluid mosaic model is made up of a blayer of lipids integrated with proteins the thicker the myelin in other words the more layers of cell membrane making up the more advantageous it is to the one advantage is the regeneration of severed axons in the periphery advantage is an increase in the speed of the action potential along the axon the rest of this presentation will concentrate on the increased speed of action potentials down the length of the mileinated axon here is the neuron and you can see the repeated schwan forming the mile note that there is a small space between the cell where the axon is not covered by the neuro cell these spaces are called nodes of a thank you from what you already know action potentials occur at the axon hill and continue to be repeated away from the cell body much like dominoes falling one after another an action potential starts on a polarized membrane which is7 It stimulus causes the sodium gates to open oh oh that's all we get i don't know what happened well you could finish this right signal stimulates the sodium gates to open and then what happens sodium rushes which direction into the cell right depolarizing the membrane right and then it goes until it reaches a closing point right passes threshold opens up the voltage gates goes to positive 55 those sodium voltage gates close quickly the slow potassium gates have already opened they stay open now they're repolarizing because potassium is going which direction out taking positive ion out leaving behind a negative balance or a negative environment they close a little slow so as they close they overshoot that's hyperpolarization creating your relative refractory period and then sodium potassium ATPAS resets the three versus two movement of sodium and potassium okay cool so let's look at this diagram kind of similar uh text that we've seen before in coloration we've got this diagram here kind of showing the myelin we've got uh the neural lema and the Schwan cell and you can kind of see this explosion implosion I should say of sodium ions rushing into the cell that's only happening at the nodes and as that signal propagates nothing happens underneath the Schwan cell it happens right here again so this signal if you if you look at the signal like in green is the excitatory red is where the action potential is happening and yellow is the refractory period and you can kind of appreciate the propagation of saltatory conduction is it kind of skips underneath the myelin and goes to the next node where you get the exchange of ions you only have the exchange of ions at the nodes because that's the bare spot of the membrane that has a transmembrane protein embedded in it that's the sodium voltage gated channel does that make sense so if you chew these up during multiple sclerosis you break those down you actually create a situation where and in this diagram this is a paper from um Nature Reviews neuroscience this is not the paper that I'm going to have you review but it's an older paper i'm going to have you review a more recent paper but you can see the immunohistochemistry on the far right you can see the schematic diagram on the left that's a representation of each of these stages and if you hone in on this upper right picture the milein is actually colored in sort of this white hue or white cloud so you can kind of appreciate on this side and this side the axon has a bunch of myelin and the nav 1.5 in the Casper these are functional units of voltage gated sodium channels the red and the green so in a healthy nerve that's mileinated right here at the nodes and the cartoon diagram is showing uh inserted channels do you see these inserted voltage channels that only here at the nodes and the aminoistochemistry is demonstrating yeah there's no there's no voltage gated sodium channels underneath the myelin i can confirm that by the red and the green staining but as I start to deteriorate as the progression of multiple sclerosis continues and it demyelination is happening you lose the myelin so what you do is your body compensates by upregulating the insertion of these voltage gates so that you can still use the nerve so you can appreciate in this panel more red and green as this continues more red and green as you lose myelin at some point your body can't keep up with it you're losing too much myelin the nerve kind of deteriorates and you lose the ability to send the signal and that's the debilitating disease of MS so it manifests itself in a lot of muscularkeeletal problems where patients begin to have gate issues or walking issues they might need you know a cane and then a walker and then they can't walk anymore and they may have respiratory failure as the disease progresses so multiple sclerosis it's an autoimmune disease uh leads to problems controlling muscles also blindness as the uh neurons in the vision pathway deteriorate and it's the immune system that's attacking the myelin sheath that goes in the blank so revisiting this uh topic we kind of already talked about this but just revisiting it as we wrap up um myelin isn't the only thing the diameter also influences it so this is the second time we've kind of introduced this concept the larger the diameter the what faster the speed of transmission so if this is looking down the diameter of the axon faster versus slower and the analogy we used was the milkshake straw so what's going on at the synaptic knob so we're back to in this picture we're back to the um post synaptic uh neuron and as we look at hang on the postsaptic neuron we've got this side of the postnapic neuron here's the presinaptic neuron so this whole thing is called what well it's not a neuromuscular junction because we're neuron to neuron right so this is just a syninnapse and we've got this neuron and I want to convince you that this neuron is a cell and then we've got this neuron and convince you that this neuron is a cell but these are two identical looking neurons you can see mitochondria you can see microtubules inside uh the cytokeleton you can see vesicles that contain neurotransmitter dumping their contents and then a neurotransmitter receptor on the opposite side so we have an electrical signal that moves to a chemical signal and then back to an electrical signal the neurotransmitters that we've focused on exclusively to this point have been what cetylcholine mostly and epinephrine right norepinephrine right but what is the purpose of having this structure this syninnapse why does it exist what did we say is the purpose of having the syninnapse at all do you guys remember what greater control you know it's like having stop lights right you can control the traffic you can control the signal so needless to say the chemicals that cross the synaptic clft are known as neurotransmitters and there's a whole slew of them there's over a hundred known neurotransmitters that our body utilizes i'm not going to ask you to memorize them all but they can be excitatory or they can be inhibitory remember that chonergic synapses use what cholonic what do they use acetylcholine right in adinergic synapses use what norepinephrine right but so here's our acetylcholine here's our norepinephrine but you can see a whole other slew of neurotransmitters like for example um here's dopamine serotonin a lot of these neurotransmitters actually help facilitate different types of moods or your uh state of mind you can see uh a GABA glycine aspartic acid glutamic acid over here we've got enkephilins and endorphins these neurotransmitters give you a sense of invincibility this is what's being released when you have like a runner's high you're exercising and all of a sudden you feel this like feeling of euphoria these are natural endorphins or enephilins that are being released in your body they're natural painkillers um substance P we'll learn about this later but substance P is what is utilized to submit pain responses back to the brain substance P so many different neurotransmitters for many different purposes control as well as variety we're complex organisms folks so these neurotransmitters the way they operate mechanistically is one of two processes they're either ionotropic or the metabotropic quite simple the definition if they alter the membrane potential they're considered ionotropic they move ions ionotropic so like acetylcholine is ionotropic it moves ions if it stimulates a second second messenger system like cyclic AM it's going to be called metabotropic like stimulating some metabolic process in the cell so you can kind of see how this lian binds atp is utilized to make cyclic AMP and then you get gene transcription that ensues enzyme synthesis and then you make some metabolic effect so either ionotropic it stimulates ions to move or metabotropic using cyclic AMP as a second messenger system okay question for you as we wrap up for today during saltatory conduction action potentials jump from where to where D one node of Ranvier to another well done you'd be wrong if you said one note of Ranir to another but we'll talk about that later any questions okay stick with me