Neurology | Resting Membrane, Graded, Action Potentials

What's up, ninja nerds, in this video today? We are going to talk about

resting

membrane

potentials

,

graded

potentials

and

action

potentials of neurons guys, before you watch this video, hit the like button, hit the subscribe button, comment in the comments section and all. information from all our social media platforms instagram facebook patreon all of that will be listed in the description box go check it out okay let's go ahead and get started okay nurse ninja so what do we have to do when we talk about? all these

membrane

potentials inside a neuron is that we have to get closer to the neuron, we are really talking about all that cellular processing and ion movement that is happening here, so the first thing we have to say is that we are talking about all these potentials of a neuron. neuron, we have to start with the

resting

membrane potential.

Now the first thing we need to do is give a basic definition of resting membrane potential. So how would you describe the resting membrane potential? What is it? The resting membrane potential is the voltage difference between both sides. this cell membrane when the cell is at rest, that's it, it's the voltage difference across the resting cell membrane and the next thing you need to remember is that yes, we're talking about this resting membrane that potentially exists in neurons. , but Resting membrane potentials can exist in every cell, so it exists in all cells. It is very important to remember that in this case we are only referring to it in the neurons.

Well, the next thing you need to know is what is this actual voltage if I could put a value, a number, to this voltage difference across the resting cell membrane in a neuron, what would it be and it's actually a range, so I'm going to abbreviate the resting membrane potential. In general, this is a range. Now, most textbooks like Maria says. It's about negative 70 millivolts, which is kind of about average. Other textbooks will take you a little further away from that. The best way to cover all bases is to say that generally it could be between negative 70 millivolts and negative 90 millivolts with most.

Textbooks supporting negative 70 millivolts is that kind of average number. Well, that's what we know about resting membrane potentials. Now what we have to do is understand what we are seeing because we are approaching a neuron. So what I'm really doing here is taking a neuron. We're looking at a neuron like this. Here will be your axon, your cell body, and then here we will have the axon terminal, okay? What I'm doing is I'm zooming in on this portion of the cell membrane and we're looking at that, well, that's what we're doing here, so we're actually zooming in on the cell membrane of this neuron and looking at the activity, so you have to have a question here, how the heck does your resting membrane potential get from negative 70 millivolts to negative 90 millivolts? that voltage from negative 70 to negative 90 is sodium and potassium atpases, what these sodium and potassium atpases do is they are very interesting and very smart and they pump three sodium ions out of the cell, so three cations are ions positives out of the cell and then pump two potassium ions or two cations into the cell. now take a look at this, let's assume for a second that we are starting with a particular voltage, let's say we are starting with zero millivolts, that is our imaginary starting point of how we are going to get to negative 70 millivolts, so we will start with zero millivolts Now, when these sodium and potassium ATPases are working, they are pumping out three positive ions and they only bring in two positive ions because of that which makes the inside of the cell just a little bit more negative not significant just a little bit negative maybe just takes it away. zero millivolts to negative five millivolts, so it's not a big change, but that's obviously due to the sodium and potassium atp ases, so these will be one of the reasons okay, so what are they called here ?

They are called sodium and potassium atpases. That's one of the functions of the sodium and potassium ATPases is to help make the inside of the cell slightly negative. The second reason why they are so important. is that they set the concentration gradient for sodium and potassium now what are they doing to sodium? These pumps are pumping out the sodium, so what is that doing that increases the concentration of sodium outside the cell and conversely, the concentration of sodium inside the cell will increase? be lower, okay, now you are also concentrating potassium in the cell, you are pushing a lot of potassium in, so what you are going to do is increase the concentration of potassium inside the cell and in contrast, there will be less potassium outside the cell. cell, so there are two functions.

Of these sodium and potassium ATPases, one is that they generate a small negative charge inside the cell at rest, the second reason, the second thing they do is generate a concentration gradient for these ions to move and that will be important for the Next two things that contribute to the resting membrane potential, okay, beautiful, now the second thing that contributes to the resting membrane potential are here, these blue channels, okay, and that brings us to our next discussion, there will be many different channels within a neuron that contribute to all of these. different resting potentials

graded

action

when we talk about resting membrane potential these blue channels here are very special types of channels they are called leaky potassium channels and what that means is that they are these little proteins embedded in the cell membrane and they are always there. open and allow ions like potassium, in this case, to enter and leave the cell freely and the key word here is passively.

Well, now these potassium channels are very leaky, so that will allow ions like potassium to move, which direction would they move? Potassium wants to move well, remember what we just said here with concentration gradients. Potassium is higher inside the cell due to the sodium and potassium rhythm. So if potassium is higher outside the cell and lower outside the cell, where does it go? to want to go, you're going to want to get out of this cell and get out, so all this potassium is going to start leaving the cell, so let's look at this here that the potassium is leaving the cell and how it's leaving, it's leaving, what's moving into down in your concentration. high concentration to low concentration gradient from intracellular fluid to extracellular fluid okay, beautiful now that these positive ions, these potassium ions are coming out, what's happening inside the cell, great question guys, potassium in It is actually bound normally inside the cell. to an anion, you see this, I'm going to represent it as a good, it's just your gene, your non-specific anion, negatively charged ion, what are these anions and why do I mention it?

These anions can be two types, okay, these anions that I'm representing here as a negative sign, there can be two things: one is that they can be phosphates and you know, phosphates are actually negatively charged ions and they find it very difficult move out of the cell due to that charge. The other thing, let me put my bookmark here. The other thing here will be proteins, proteins, you know, proteins are made up of amino acids, tons of amino acids and these amino acids have a lot of negative charges, well that's another reason why they can't leave the cell, but what? what did I do?

Let's say what's common with these, this has negative charges, this has negative charges, that's what makes it an ion. They love to interact with potassium, which is a cation, so every time the potassium goes, you think oh, the anion is going to go too, no, it's too big. and it is too charged to leave the cell, so every time potassium leaves, it leaves an unoccupied anion and now, every time potassium leaves, it leaves an unoccupied anion and makes the inside of the cell more and more negative , so now this is super negative inside the cell, what voltage you're not going to believe this, but if potassium could, it would move out of the cell until you got that voltage somewhere around, say, negative 90 millivolts, Let's say you took the inside of the cell and we flipped it from negative five all the way to negative 90 millivolts, that was due to these leaky potassium channels, now the last one that contributes, so we have the sodium and potassium pumps, the channels. of leaking potassium, the last one that is going to contribute to this here.

The resting membrane potential is your leaky sodium chambers. Now remember that there are other ions that can move in and out of these cells. Calcium chloride. I'm only considering considering sodium and potassium as the main ions because those are the most important in this case, but note that you could also consider calcium and chloride, but for now what I want you to remember is that one is the Sodium and potassium ATPases, the second is the leaky potassium channels, the third here will be the leaky sodium channels, now these are leaky. Again they allow sodium to enter or leave the cell, but again, where is the sodium concentration gradient?

We already said that it is higher outside the cell, so if the sodium concentration is higher outside the cell, in contrast, it is lower inside the cell, then where? Will sodium want to move? The sodium will then want to move into the cell down its concentration gradient. As sodium enters the cell down its concentration gradient, it makes the inside of the cell positive, but here's the most important thing. I can't emphasize this. In this case, this cell is much more permeable to potassium than sodium, so it will allow tons and tons of potassium to leave the cell, but will only allow a little bit of sodium to enter.

So because of that, we have to write this, that potassium, when we talk about permeability, we'll put a little heading here, permeability factors, just when we talk about it with the cell, potassium is significantly more permeable than what is sold . much more permeable to potassium than sodium, so potassium will make a big change, like going from minus 5 to minus 90, but not much sodium goes in, so it may not be that significant of a change, maybe it's just takes us from negative 90 to negative 70 millivolts and we have reached our resting membrane potential, so to summarize what are the three components that really help us with these sodium and potassium atpases, the leaky potassium channels, the sodium channels leaky and if you really wanted to add others in the leaky calcium and leaky chloride channels, but the same concept applies.

The last thing we need to talk about is because this shows up on your exams. A lot is learning how to calculate what is called the nernst potential for calcium, potassium and sodium chloride. We're literally going to go over the equation quickly, so when we talk about nerd potential, I really just want you to know the equation and then it's really a plug and go thing, from here it really doesn't get much further than this. It is important that you know when you use nursing potential and what the proper formula for nursing potential is. So the nerd potential, the first thing you need to know is when you use it, when you use it and that's a very important question.

Take, for example, potassium, in this case, okay, potassium, we know that it leaves the cell according to its concentration gradient, but as it moves out of the cell, the inside of the cell becomes positive and , therefore it becomes more negative, right? that negative charge inside the cell. wants to attract some of the potassium back into the cell, which is called the electrostatic gradient, so the potassium leaves the cell following its concentration gradient, but it sort of comes back into the cell following its electrostatic gradient, the moment when that potassium moves equally. or it is as if there were no net movement of potassium leaving the cell down its concentration gradient or entering the cell down its electrostatic gradient as long as those two are equal, that movement has reached the nerd potential, like this we write it like this Whenever potassium leaves the cell is equal to the potassium that enters the cell and leaves through its concentration gradient, to its concentration gradient and enters the cells through its electrostatic gradient, then we can use the equation well, then the next question is what? is the equation that equation is like this we are going to write it for potassium and for the voltage, well, the equilibrium or the voltage that potassium can generate across the cell membrane at rest is equal to 61.5, which is a constant divided by z, which is basically the charge of the ion in this case what is the charge of potassium plus one which is 61.5 divided by plus one 61.5 so we can get rid of that by multiplying by log base 10 the ion concentration of potassium outside the cell and again this is a value that you would get from a table or a textbook and we're going to put here 5 is the concentration of potassium outside the cell, so this is here, something else here,this is the concentration of potassium outside the cell during the concentration of potassium inside the cell and again this could be 150 correct if you calculate all this it will come to around negative 90 millivolts which tells you that the potassium will move out of the cell until it moves out of the cell downwards. concentration gradient until the inside of the cell becomes negative 90 millivolts and then that movement down its electrostatic gradient keeps it at that kind of equilibrium point.

Now the same concept applies to sodium if you wanted to. To calculate sodium, I say the equilibrium potential of sodium is equal to 61.5 divided by z, it's plus one, so I don't need to multiply the log by base 10 and then again you would have to pull this number out of a table, uh and Generally, that's like 140 for the sodium concentration outside the cell and then about 10 for the sodium concentration inside the cell and then again, if you calculate all of this , you'll get your sodium balance potential somewhere around positive 70 millivolts now. If you add both negative 90 and positive 70, you're basically saying that your resting membrane potential is the equilibrium potential of potassium at the equilibrium potential of sodium and if you did that, what would you get positive?

You would get negative 20 millivolts. 90 plus 70. but remember what I said, it's a matter of permeability, so there will be a lot more potassium coming out of the cell, so the cell voltage will be closer to this potassium equilibrium potential, so always let's calculate this If you were to take a percentage and say well, let's say this cell is 90 percent permeable to potassium and only 10 percent permeable to sodium. If you calculated all of this and then added them together, you would probably get roughly around 70 negative millivolts and That's how we really get into the nitty-gritty of how to calculate these voltages.

Alright, pretty good potential graduates. Okay guys, so we talked about resting membrane potentials. Okay, now what we need to do is take that resting membrane potential. Negative 70 millivolts we said about how we realized that, what we already talked about now what we have to do is bring those negative 70 millivolts to a threshold voltage, we are approaching a position of action, we are building a story. what we're doing here, okay, now what's the purpose of graded potentials, the real underlying purpose is to take the resting membrane potential clockwise and bring it closer to the correct threshold, so if you're trying to get it closer to the threshold voltage, which?

Is that voltage what we need to open voltage-gated sodium channels in the axon? That threshold voltage is generally about negative 55 millivolts. If I want to take my negative 70 millivolts to negative 55 millivolts, I need a slight depolarization, but you know what else? Sometimes we don't want to stimulate an axon, sometimes we don't want to stimulate an action potential, so another aspect of graded potentials is not just depolarizing it or bringing it to threshold, but sometimes we can take that resting membrane potential at 70 negative millivolts and actually, move it away from the threshold and maybe take it even lower than the resting membrane potential, and we could reduce it to negative 90 millivolts, this is called hyperpolarization.

Okay, it's hyperpolarizing the cell and making it even more negative. There are particular names for these and that's what we really have to discuss whenever you take the resting membrane potential and you try to bring it to the threshold, you're trying to excite this cell, this neuron and we give a term for this, we call it an e p sp an excitatory postsynaptic potential, but then if you have another neuron that you're actually trying to inhibit, move it further away from threshold. Now look how much further we are from the threshold, we are at negative 90, it will be very difficult to stimulate this. neuron, so if you are actually trying to inhibit this neuron, this will be called an ipsp, an inhibitory postsynaptic potential.

Now to give you an idea of ​​what we're really zooming in on and looking at here, let's say we take another neuron here's our neuron, okay and here we're going to have another neuron, we're going to have a neuron here acting on this guy and then we're going to have another neuron. here acting on this, what we are doing is we zoom in here and take a look at this part here, we zoom in here on this cell membrane and we look at how these neurons influence this postsynaptic neuron, so again in terminology, these are called neurons presynaptic because this space here is called a synapse this here is after the synapse so this is called a postsynaptic neuron so you have postsynaptic neurons presynaptic we are approaching that synapse well, the first thing I want you to know is that we are going to have have something that excites the cell then what we are going to do is give a stimulation signal here we are going to call this neuron here this neuron that is going to try this presynaptic neuron is going to try to excite this cell, this postsynaptic neuron and the way it will do it is by releasing a particular neurotransmitter.

Let's choose in this case a stimulatory neurotransmitter like glutamate. You know, glutamate is a very good stimulator within the central nervous system. And? What we're going to do is have the glutamate bind to this little receptor site. Look, there's a little pocket there, that little pocket is important because once the glutamate binds to it, normally what happens is these channels close and I have to talk about what kind of channel it is normally, there's like a little door that blocks it, there is a small door that blocks the entry of ions, but once the glutamate binds to this small pocket, it lifts this door and now what was closed. that type of porous surface now opens now look at the door, it opened and now what happens is this opens the channel for ions to flow in what type of ions any type of cation usually maybe it's sodium that will flow in this cell maybe it is calcium that will flow into this cell and as the sodium ions and calcium ions start moving inside the cell it makes the inside of the cell positive remember what the voltage was previously inside the cell cell we were in.

Negative 70 millivolts and now what's going to happen is these positive ions moving into the cell are going to try to start moving the inside of the cell into that positive range. More positive, maybe negative 55 millivolts is what we want to get right. That's what this epsp means: it brings positive ions into the cell, how does it do it by binding the neurotransmitter glutamate to this type of channel? What is this channel called here when a ligand, neurotransmitter or chemical binds to this pocket of this channel and? opens it, this is called and has many names, but I like to refer to them as ligand-gated ion channel.

Okay, beautiful, so these are your ligand-gated ion channels and they're going to be one of the things in this case. the stimulating neurotransmitter bringing in positive ions will lead to this epsp that we talked about and we'll graph it in a second. In the other situation, we have to have the opposite action, the ipsps, so now what we are going to do is we are going to have an inhibitory neurotransmitter here and this inhibitory neurotransmitter will release a particular neurotransmitter that will commonly cause inhibition, what is this type? This could be something like gaba gamma-aminobutyric acid, gamma-aminobutric acid or gaba is actually going to bind to this little pocket and again let's say this little pocket had this door closed, okay, but every time gaba binds, it stimulates this type of channel and then what it does is it opens that little door that was previously blocking the opening and what does this allow chloride ions to enter the cell, so chloride ions enter the cell or can it allow that potassium ions leave the cell now?

If potassium ions leave the cell, what do they leave behind? Remember what potassium normally does. attached to an anion and these anions are proteins and phosphates and they can't leave the cell so every time potassium leaves it leaves the anion and if you leave the anions behind that makes the inside of the cell negative if you bring chloride ions which are negatively charged ions into the cell, what is that going to do? Make the inside of the cell negative. What was the previous voltage inside the resting cell before we had this gaba acting on this ligand-gated ion channel?

It was negative 70 millivolts. What happened is that you brought in all these negative ions in the form of chloride or in the potassium ions, you left cations that made the inside of the cell negative and hyperpolarized it and took it from negative 70 to negative 90 millivolts, let's say it's good. Made it even more negative, that's called i ipsp. Now this is what a constant battle is. There is a constant battle between this neuron. You can have multiple stimulating and inhibitory signals acting on this neuron. Your goal is obviously to have more epsps than ipsps, but. If you were to look at this on a graph on the x axis we have time in milliseconds and on the y axis we have millivolts, let's say here is my resting membrane potential, what was that voltage?

We said negative 70 millivolts, right? what is my threshold my threshold is negative 55 millivolts that is where I want to get to be able to open those voltage dependent sodium channels in the axon trigger an action potential so that will be this pink line this is my threshold potential how do I do? we try to get there, epsps, well, this is what we want, we want stimulating signals, we don't want so many inhibiting signals, but in life that's not how everything always works, so sometimes what can happen is that maybe you have a correct epsp and that epsp is getting close to that threshold potential, but it's not enough, if you don't reach the threshold potential, you don't get a correct action potential, it's kind of an all or nothing phenomenon, so maybe What happens is that you get to this point and you try it. to properly trigger this depolarization and it just doesn't come right and then maybe what happens is you get another epsp that kicks in and maybe you get a little bit closer but still don't hit that potential threshold at the same time.

You could also be having what more, you could also have these ipsps tripping, they could also be trying to lower the voltage and then another one trips and takes it down, so it's a constant battle between these two, how could we get the epsps and the ipsps? To get to this point where I can reach the threshold, the goal is to have more epsps than ipsps, that's pretty much the end goal, if I can get more eps. PS, you can imagine if I had enough eps to advance. one on top of the other, I could eventually reach that potential threshold, well how can I make these eps rates just add up or add on top of each other?

I'm really glad you asked, there's a type of thing called sum or wave summation which is what I want to talk about now, so let's come down here and take a look. We're going to talk about two types of sums that we can get, like little EPSP add-ons to get that potential threshold because that's our goal we want this, how can we get there so well? The first one here is called temporal summation temporal summation and temporal summation it's like a mosquito at a barbecue just bothering you to death right, it's just constantly bothering you that's what this is our postsynaptic neuron this neuron here here is our presynaptic neuron and let's say that it's going to release glutamate correctly so this is a stimulator we'll put that stimulation signal here it can fire once correctly if it fires one more time what is it? here the resting membrane potential what is our target threshold potential here is where we want to get to this is negative 70 this is negative 55. let's say this presynaptic neuron fires it triggers an epsp it gets there it doesn't reach the threshold and then it fires again it's a mosquito just bother you add on top of that one doesn't get there send another stimulus add on top of that and boom we reach our threshold voltage once you reach that threshold voltage you can activate the action potential so that's the goal here is that temporary The summary is that it is a presynaptic presynaptic spell that the wrong presynaptic neuron repeatedly stimulates a postsynaptic neuron and then every time you repeatedly stimulate that postsynaptic neuron, it will be added on top of that, so again let's say here's one stimulus, two stimuli , three stimuli. that takes me to my threshold potential that's how this temporal summation works what's the other type of summation another way we can take that resting membrane potential to the threshold potential it's called spatial summation spatial summation now spatial summation is a similar concept but now instead of one neuron just bothering you, you will have three neurons firing simultaneously, so you have three presynaptic neurons, it will fire, fire, and fire all simultaneously if that's the case, so if I all and I have all these, here's my resting membrane potential at negative 70 millivolts, here's my threshold potential at 55Negative millivolts, if I have all three adding together and adding all the shit together, I'm going to hit that potential threshold, that's how it works. as long as it has two correct forms, one is temporal, one is presynaptic only on a postsynaptic neuron or a spatial summation which is multiple presynaptic neurons firing simultaneously on a postsynaptic neuron and finally these epsps can be summed so these are the ways we can get the membrane at rest. potential at negative 70 to the threshold potential, which is negative 55 and the way you can do that is by having more epsps than ipsps.

How do you get so many epsps? One is just constantly firing from one neuron to another or multiple neurons firing simultaneously in one neuron and you can add up those epsps to go from resting membrane to threshold potential, boom and action potential, all good ninja so we are almost at the end of our story, we are at the action potential, we want graded resting membrane potentials. We are now at action potentials, so how can we get to this point? So we started with the resting membrane potential, which was at what negative 70 millivolts we said we hit the actual threshold potential, what was it? our threshold potential our threshold potential was negative 55 millivolts, how do we get from the resting state to the threshold?

We did it by the process of higher potentials, the epsps are more correct than the ipsb or we add them now, the reason we have stressed so much About this negative voltage of 55 is that these purple channels are very sensitive to voltage, particularly to that voltage. Let me show you another diagram of what we're looking at here before we start digging into this thing we're looking at. a neuron here is the cell body here is the axon and then here the terminal will be right now we have focused mainly on what we talked about presynaptic neurons with the epsb and the ipsb.

We take a look at the resting membrane potential. now what we're doing is we're looking here at this point, this is the axon hillock, then all of this down here is our axon and then this last point here that we're going to talk about is the axon terminal, so this is the end point of our real journey here inside the neuron. Well, this point here is actually of great anatomical importance. You see how the cell body type tapers towards the axon. There's a particular name for that, I like to call it trigger zone. but textbooks love to call this the axon hillock the axon hillock is its firing zone the firing zone, which means that once it has reached a particular voltage within the cell, it can trigger a potential of action by opening these voltage-gated sodium channels that are highly concentrated in this area, so here we have it, this voltage-gated sodium channel, this voltage-assisted sodium channel is normally closed and we'll talk about how it closes, there is different types of gates, we'll get to that later when we're done.

Let's go with this last one, this little graphical representation for now just listen and then whenever we go over, it will make sense once you reach a particular negative voltage of 55 millivolts, what that does is it activates these voltage-gated sodium channels, particularly what is called activation. doors on the outside and once these activation doors are open, the sodium ions will start to come in very, very powerfully now, when the sodium ions move into the cell, they make the inside of the cell super positive, super positive, for example, you were at negative 55 millivolts when this Sodium comes in quickly, it takes the voltage from negative 55 millivolts to positive 30 millivolts.

Shit, it really flips the script, doesn't it? Every time sodium comes in, it actually comes in and runs into the cell until it goes from negative 55 to positive 30. why positive 30 the reason is that once you have positive 30 millivolts there is another gate called the inactivation gate of this voltage dependent sodium channel that closes and then because of that the sodium can no longer enter beyond that voltage, so you can remember two voltages negative 55 opens the voltage gating gate you get a sodium channel and a positive 30 closes the voltage gated sodium channel inactivation gate and that's why these numbers are coming out right now that we've done it, guess what happens to these positive ions that are on this side of the cell here, guess what they're going to do, they're going to come here and they're going to create a particular voltage to bring it to the threshold on this voltage-gated sodium channel. in particular, once you get to this, it was at negative 55, it will open and the sodium will quickly enter the cell, as the sodium enters the cell, it will make the inside of the cell super positive and change the voltage from 55 negative to 30 positive millivolts. and again these positive ions are going to start moving down the axon.

You see how it moves down the axon. These positive ions are going to bring the inside of the cell here on the right, negative 70 millivolts, bringing it closer to the negative threshold 55, activating the voltage gate of sodium channels, the sodium will quickly enter the cell, it will make the inside of the cell super positive and change the script here and change from negative voltage 55 to positive 30 millivolts now there is something really important that I want you to see here there is a trend that see how we start the axon hill we reach that particular voltage we open the voltage gate of the sodium channels sodium came in when it came in it flipped the inside of the cell it made it positive what's the next thing it did it didn't just make the inside of the cell positive or another term every time it makes the cell inside the cell positive it depolarizes, where is that depolarizing or positive wave that moves down the axon?

That's important, so this is called an action potential, which is the depolarizing or positively charged wave. wave that moves down the axon towards the terminal bulb now this is where we have to go to the next part these voltage-gated sodium channels will actually do what they will make the inside of the cell positive every time they enter, well, You know? There's another channel here, another special channel that actually only activates whenever you reach positive 30 millivolts, so it's called a voltage-gated calcium channel, so it's called a calcium channel. It's a voltage dependent one that only activates when you reach positive 30 millivolts, so sodium. will rush makes the inside of the cell positive around positive 30 opens these voltage-gated calcium channels and calcium will rush into this axon terminal when calcium rushes into the axon terminal there is a specific reason for that, You know, this particular protein traps proteins that are present in these vesicles and then present in the cell membrane of this axon terminal, different types of trap proteins, what calcium does is bind these two proteins and when it binds these two proteins, Guess what happens, the synaptic vesicle fuses fuse. with the cell membrane and when that synaptic vesicle fuses with the cell membrane, what do you see, oops, and then what happens?

All of these neurotransmitters or neuropeptides that are inside that actual vesicle are released into this synaptic space and what will they do? get it right, maybe there's another cell and then what happens is this neurotransmitter binds to this particular receptor, okay, and if this neurotransmitter binds to this particular receptor, it can exert its effects on this other cell, like this I want you to see how we start. with the resting membrane potential reaching the threshold, an action potential is generated, the action potential moves down the axon. fusion of the vesicles with the cell membrane and then the exocytosis of the neurotransmitters now we have stimulated this cell to look like a son of a gun now what we have to do is make the inside of the cell relax, we have to bring it make it more negative again now there are terms that we have to understand well we use this term depolarize I want to make sure that we are completely clear on what that means what does it mean depolarized means that you are making the cell positive You are making the inside of the cell positive, that It could mean that you started out negative and became positive or you went from really negative to less negative.

The point is that you are making the inside of the cell more positive than the other one was before. The term we need to keep in mind is called repolarization, so when you repolarize the cell, what is that? So, you are repolarizing the cell correctly. Basically, let's say you started with a positive voltage, you're taking that positive voltage and you're going back to a negative voltage, but particularly that negative voltage that you want to get to is the resting membrane potential, that's really what repolarization is the reason. which is why I want to make it so clear that repolarization returns to the resting membrane potential, which is negative.

It's because there's another thing we talked about called hyperpolarization and when you hyperpolarize your cell you take a cell that's already negative and you make it even more negative, well those are the things that need you to understand, they depolarize, they make it positive. , they repolarize. We are going from positive to negative or the resting membrane potential is hyperpolarized, you are making the cell even more negative than it already is okay, beautiful, well, we have depolarized this axon a lot and then the axon terminal, now we have to repolarize it. Going back to the resting membrane potential, how do we do that?

I'm glad you asked. Look at these 30 positive millivolts. These positive 30 millivolts can inactivate the sodium channel inactivation gates, but you know what they do. They activate these voltage-gated potassium channels and then these voltage-gated potassium channels get what they allow, they allow potassium to leave the cell and when this potassium leaves the cell, what happens inside the cell? All of these positive ions escape from the cell while that happens. it takes the voltage from where it was positive 30 millivolts, the potassium is going to go out and out and out of the cell and it takes it until it takes the voltage from positive 30 to negative 90 millivolts to negative 90 millivolts, so you're really flipping the script. .

Here right now, the inside of the cell is going to be super negative. Well, the same thing here was positive, 30 millivolts, so we were here at positive 30. It stimulated the potassium voltage gate. The left potassium made this portion of the axon negative. We come back here, this part is positive, right, the voltage-gated sodium channel was activated, the sodium coming in made the inside of the cell positive, 30 millivolts positive which activated this voltage-gated potassium channel after it was stimulated that voltage heated potassium channel, what happens? Potassium will leak out of the cell and as these positive ions leak out of the cell, what does it do?

What makes the inside of the cell negative? How negative. Well, it was positive 30 millivolts, it takes it to negative 90 millivolts. Now the following happens. Previously, we were branching, so I can show you what happened previously. There were 30 positive millivolts here that activated voltage-gated calcium channels, depolarized calcium, and triggered neurotransmitter release. This calcium can't be here just because one neurotransmitter is being released all the time, we have to prevent these voltage-gated calcium channels from being open so that we can block calcium entry and prevent more neurotransmitter from being released, so let's assume that that Voltage-gated calcium channel was previously what positive voltage 30 millivolts because that's where we were before.

Well, what happens is when you have these voltage-gated potassium channels open and the potassium comes out of that potassium as it comes out, the inside of the cell is going to be negative and that actually kind of brings the inside of the cell out of the way. that 30 positive millivolts too negative 90 millivolts guess what those 90 negative millivolts will do to that voltage dependent calcium channel it will inhibit it once that voltage dependent calcium channel is inhibited the calcium will no longer be able to enter this cell if not calcium can be brought to this cell. What is going to happen?

Could it join these synaptic vesicles here and fuse them with the cell membrane? The neurotransmitter will not be released. No. This is how this whole process happens, so what I want you to understand is that this is not happening piece by piece and the way we talk about it, it actually happens like this: you reach the threshold, you open the voltage. The closed sodium channels open pop pop pop pop all the way down, okay, but while this is happening this depolarizing wave is moving down the axon, guess what is falling right behind it, the repolarizing wave is also following it to bring back the inside of the cell. to the resting membrane potential now you'll notice something you'll see here that I actually put it at negative 90 millivolts.

Well, we said that the resting membrane potential is 70 millivoltsnegative, but what happens is that potassium comes out of these voltage dependent. Potassium channels take a little while to close, so a little more potassium than usual can leak in and make the inside of the cell a little more negative and hyperpolarize it a little, but again, what three things contribute? because the membrane is at rest, but returning it to the resting memory potential, its sodium and potassium pass through its leaky potassium channels and its leaky sodium channels, so eventually that negative 90 will go back to negative 70 and it will go back to the potential. membrane at rest, this is how an action is performed.

The potential happens now, what we have to do is build on everything we've talked about and talk about it in a graphical representation. Good, engineer. So what we're going to do now is put all of this together. That's a good summary, but I'm going to have to add another thing that we said we were going to talk about, which is to talk in a little more detail about those voltage-gated sodium channels, just to add a little bit more. additional fact on that so here we're going to have our graph okay here on the x axis we have time here on the y axis we have voltage remember what we said was our resting membrane potential negative 70 millivolts or so correct that was our resting membrane potential well we said our goal what would actually be good here what led us to the resting membrane potential sodium atpases potassium leaky potassium channels leaky sodium channels which was more permeable potassium or potassium sodium now what The next thing we said we had to do is go from the resting membrane potential to the threshold potential, that was our next objective and the threshold potential that we said was negative 55 millivolts which took us from the resting membrane potential to the threshold potential our epsps correct how did we get enough eps ps to reach the potential sum threshold?

What are the two forms of temporal or spatial summation or simply general wave summation? What were the waves? What were the types? of potentials that were trying to inhibit it and move it away from the resting membrane, its ipsps were trying to hyperpolarize it, but if we are trying to stimulate, let's say we start here at the resting membrane, we have an epsp, we add it, we add eight, we add . we reach the threshold potential once you reach the threshold potential what voltage gated channels open in the axon hill the voltage gated sodium channels once those voltage gated sodium channels open the sodium will move toward the cell until it reaches approximately what voltage approximately positive 30 millivolts, well, we said we were going to talk about what these voltage-gated sodium channels look like.

Now it is important to know what they look like in the resting membrane potential at the peak of depolarization and then what they look like when they try to move forward. Back to the resting membrane potential, okay, so let's say we start here with the resting membrane potential, so at this point, what would those voltage-gated sodium channels look like? If you took a look at one here, it would look like this, here's your channel. It has two doors, one door is on the outside of the cell, so let's assume that here is our cell membrane. Okay, you have a door on the outside of the cell and this door will usually be closed at rest, this is called an activation gate, so you have another door on the inside of the cell and this door is usually open whenever the cell is at rest. rest, that is called inactivation gate.

Well, this is what it will look like at rest. Now what happens is once you reach the threshold potential, once you reach this threshold potential, guess what happens to those voltage-gated sodium channels, the activation gates activate and the inactivation gates will also start to activate. become inhibited and they will start to slowly close, so what will that look like when you reach the potential threshold and start going up? In this rising phase of the action potential, those voltage-gated sodium channels will look like this. Okay, now you're going to have your sodium channel here and then again your activation gates will open like this and your inactivation gates will open. it's going to slowly close so this is your inactivation gate and this is your activation gate and this is every time you get stimulated okay you reach the threshold potential and you're going through the depolarization phase this is what it would look like and again to give you an idea, here is your cell membrane outside the cells where the activation gate is inside the cells where the inactivation gate is, this is what it would look like every time the cell is whenever this is stimulated. voltage gated sodium channel, you have reached the threshold and you are moving towards the rising phase of the action potential now remember what I told you once we reach a particular positive voltage of 30 millivolts what did we say happens?

We said that those voltage-gated sodium channels become inactivated, well, it's really the inactivation gate that ultimately closes. Now if we go to the peak, then this was like here, this is the view that we got here right once we have the threshold, once we reach the peak of the action potential, so what do we get? Here is our voltage gate to the sodium channel. Now what happens is the inactivation gate is completely closed and the activation gate is completely open and again to give you orientation, here will be your cell membrane. This could be seen positively, as in this situation, here the ions can move through the activation gate.

Okay, and again, ions can't get in here. Look at this situation. You would think that these positive ions would be able to get in, but guess what is stopping them from entering the cell? The inactivation doors will not allow this because they are closed. Not allowing more positive ions to enter the cell, so this is the configuration of the voltage-gated sodium channel when it is at positive 30 millivolts, this is what it looks like at negative 55 and as you get closer to positive 30 millivolts, this is what it looks like at negative 70 millivolts, okay or resting now, once we hit positive 30 millivolts, these voltage-gated sodium channels become inactivated, what do we say?

It is activated at that time the voltage gate of the potassium channels opens when the voltage- Closed potassium channels open. What do they do? Potassium begins to leak out of the cell. Now the cell will go from positive to 32 and negative to 90 millivolts. It will repolarize as it approaches the resting membrane potential, but what do we say? It hyperpolarizes a little and becomes uniform. more negative how and why it's because those voltage-gated potassium channels are a little slower to close and so they just go down a little bit more, maybe negative 90 millivolts drop, but eventually through the sodium and potassium ATPses . leaky sodium channels leaky potassium channels over time you will return to the resting membrane potential now this is the configuration that I want you to remember well for the rest what it looks like at rest what it looks like when stimulated until it reaches the maximum potential, but this is what it will get stuck in until it wears back to the resting membrane potential, so until this voltage-gated sodium channel gets back to the resting membrane potential, it will get stuck like this, but eventually , once it reaches the membrane at rest. potential will return to this configuration where the activation gate will close and the inactivation gate will open and it will be ready to be stimulated again.

In this situation, you can't stimulate this channel anymore because it's already at maximum voltage and there's just no way for those inactivation gates to open wide, so that's why this point right at this point where we would say from here if it marked a dotted line at this point until we reach Resting membrane potential this point here from the peak of the action potential until you reach the resting membrane potential, no matter what you do, you can stimulate this with the maximum voltage possible , those inactivation gates will not activate and you We are not going to be able to stimulate this cell again, it has to go back to this configuration to be stimulated, so this period from here to here has a particular name that you should know, it is called period absolute refractory. called absolute refractory torque, what is called absolute refractory period?

I can't stimulate, no matter how hard you try, but if you think about the next refractory period, there is another one. This cell returns to rest once it reaches the resting membrane potential. What does it come back to? What do these inactivation doors open to? Open? The activation gates close and this is the configuration that can be stimulated again, but look where it is now. What do we say? This voltage could be around. This could be somewhere around. Negative 90 millivolts around that right Negative 90 millivolts is the voltage that you're at the threshold potential is negative 55. generally the only amount of energy you have to put into the cells to go from negative 70 to negative 55.

Now, if you wanted to stimulate this cell before it returned to the resting membrane potential just as it sank, you would have to increase 20 additional voltages and then the additional voltage that you would have to get from rest to threshold, so now you would have to going from here all the way to here is a lot more voltage, meaning a lot more excessive stimulation that you would have to give the cell to excite it again and open these voltage-gated sodium channels, so the period of time from hyperpolarizes the cell until it returns to the resting membrane potential, which is another name for this, it's called the relative refractory period and this is the period where you can give a stimulus and you'll be able to activate those voltage-gated sodium channels, but you have than adding more voltage, more stimulus. to go from negative 90 to rest and then from rest back to the threshold potential, that's a lot of stimulus, but it's possible, it's not possible, however with the absolute refractory period, okay ninja nerds, that covers everything They need to know about action potentials. and all these other things we talked about, okay ninjas, in this video we talk about resting membrane potentials, graded potentials, and action potentials.

I hope you like this video and I hope it helped everyone, engineers, you know what to do as always until next time. time you