Neurophysiology

Hi. In this lecture we're going to investigate neurophysiology and these are the events that happen in excitable cells. What we're about to talk about today is the depolarization and repolarization, which you already learned under muscle. So most of this should be familiar to you. We're going to add a little bit, of course, a little more specifics because neurons have a couple differences. So you already know that the resting membrane potential or RMP is the charge across a cell membrane. So if

we look at a cell membrane. We know that the inside of the cell has a negative charge and the outside has a positive charge. And since you have this separation of charges, we say that the cells are polarized. Now we also learned that the potassium concentration which was much higher inside the cell and that the sodium concentration is greater outside of the cell. We talked about leak channels. Remember that leak channels are always open they are leaky. That's why they're called leak channels. An

d all of these channels are specific for ions. So there are potassium leak channels, which you see in blue here. There are sodium leak channels, which you see as red. And what you will notice is that there are more potassium leak channels in sodium. So what that means is that the cell membrane is more permeable to potassium. Since there's more open or leaky channels, more potassium can leave that cell and potassium has a positive charge. So we're losing more positive charges than we're able to r

eplace by sodium because even though sodium will come inside that cell, there are very few sodium leak channels. So because there's more potassium than sodium leak channels, we say that the membrane is more permeable to potassium. So the inside of the cell membrane has a negative charge and the outside, as I mentioned has a positive charge and we call this the RMP. Now if I go here for one minute, if we notice the charge for a neuron is minus 70 millivolts. So the inside is negative, the outside

is positive and the RMP for a neuron, I want you to know is minus 70 millivolts. So let's go and look at. Actually we're going to look at potassium, sodium in a little more detail. But right before I do that, there is a really cool A&P Flix. So this is in Mastering in the study area where you go into, I think it's under videos and animations, I used to put it inside the lecture, but I'm not going to do that to try to keep this one a little shorter. But I highly recommend that you go into your s

tudy area at the A&P Flix and watch this one on the resting membrane potential. So we're looking at potassium and what we know is that because there's more potassium inside than out, potassium really wants to leave that cell, right. It's going to have a gradient, a diffusion gradient to leave the cell. So we say it has a concentration gradient. Now if we just let potassium keep leaving and leaving and leaving until equilibrium was reached, remember that's what happens with diffusion. It will occ

ur until equilibrium. It would actually make that resting membrane potential minus 90. Well, that's too negative and we call that hyperpolarized. So if we let potassium leave, we would lose too many positive charges. It would lower that. It would make it too negative or more negative and we say hyperpolarized, that's going to be inhibitory at a neuron. Let's look at sodium. Sodium has an electrochemical gradient. What that means is it has a chemical gradient, right? High concentration to low, mo

re sodium outside of the cell, less inside, but it also has an electrical gradient because remember the inside of that cell is negative. Now remember, one of those things, keeping it negative by the way is there's a lot of negatively charged proteins inside the cell. So that's important because when the potassium leaves, all those negative proteins are too big and they're not going to leave. So sodium really wants to get inside the cell. Very little of it leaks in at rest because there's very fe

w leak channels. But if we let it accumulate, if we never kicked it out and we let it go until equilibrium was reached, it would actually change the charge to plus 66, so obviously, that's way too positive. So what's happening, you know, why are we keeping this thing at minus 70 and it comes back to the sodium potassium pump. So sometimes you'll see it called the sodium potassium ATPase because that's the enzyme that does it. But this is the pump and its job is to basically use active transport

and it's going to kick three sodium out for every two potassium that it's going to force back in. So it's pulling the potassium. back inside of the cell and it's kicking the sodium out, so it's pumping these ions against their concentration gradient, which is why it's active transport. So the sodium potassium pump is what maintains the RMP. The RMP is negative because the cell membrane is more permeable to potassium and potassium leaves, more potassium leaves than is replaced by sodium. Now we n

eed to look at these gated channels. We kind of mentioned them briefly, but not very much. So leak channels are always open. Gated channels are different. Gated channels open or close in response to specific stimuli. So we're going to have chemically gated channels and these are channels that open in response mainly to neurotransmitters. So chemicals can do that. And these tend to be found on the cell body and the dendrites. The voltage gated can actually open and close. So we have these activat

ion gates where they can open or they can close and these are what we see in excitable membranes. We saw this in muscle, they're going to open or close in response to the charge across the cell. So when that charge across the cell membrane, we're going to measure that in millivolts. When we look at mechanically gated, they mainly respond to mechanical stimulation like the membrane moves, so like touch or pressure or vibration. And mechanically gated channels are also only found on the cell body

and the dendrites. So you might wonder, well, where are the voltage gated channels? Those are the ones that are on the axon. So when we look at the voltage gated channels, they're kind of different because they have three possible scenarios they can be in. So they can be and what's called their resting state. So in their resting state, notice they're closed, but they're capable of opening. So if there was some sort of stimulus, threshold stimulus, they would open. They could be already open. And

once they're open, they're open, they're activated or they can actually be closed, but they're not capable of opening. And that's called inactivated. So there's three general states. So remember that my chemically gated channels and my mechanically gated channels tend to be on my cell bodies and dendrites, whereas the voltage gated channels will be on the axon. Just like the passive gated channels. They're specific. There's going to be voltage gated sodium channels, voltage gated calcium, volta

ge gated potassium. So they are specific to the ion, but they open or close in response to a specific charge. Now here's where it's a little bit different. We learned about a threshold stimulus already, but what happens in the neuron is that you have to get a graded potential first. If the graded potential is strong enough, then you get an action potential. So a graded potential is also called a local potential because it signals over short distances. Anything that opens a gated channel is going

to cause what's called a graded potential, so these channels can open. But we're going to call them graded potentials and they're graded because these are dependent on stimulus strength. So you might be thinking, well you said there is an all or none law , there is for an action potential, but these are graded potentials because they are dependent on the stimulus. And So what happens is a stronger stimulus opens more of those gated sodium channels. The stronger the stimulus, the more sodium cha

nnels you open, the further the impulse spreads. If it's strong enough to travel all the way down to the axon and open those voltage gated channels, then you're going to get an action potential which is going to start down at that axon hillock. So if I go back to this picture for a minute, because it might be better to use this than for me to try to draw something, let me try to simulate what's happening here. So we're going to have, let's say we have stimulus 1 And let's make it light touch. So

something very lightly hits that little dendrite and it opens sodium channels. Now I'm going to tell you right now that we know the inside of the cell is minus 70, right, that's the charge inside and that we are going to know that threshold is minus 60. So what that means is that minus 60, all those voltage gated sodium channels fly open. Now some books will say minus 55, some will say minus 60. So either one is fine. I see a picture in your notes right now. It looks like it's minus 60, so we'l

l go with that number. So that's threshold. Because at that number they all open. So let's keep it simple. Now I'm making this up. Let's pretend for each channel that opens, one sodium comes in. So stimulus one is fairly weak, and let's say it opens three of those sodium gates. So I open 1, 2, 3, and sodium rushes in and I depolarize and it travels as the sodium rushes in. So as it moves, it's about minus 67, right? I took three away from 70. Nothing's going to happen from that because it never

made it to the axon hillock. OK, let's hit it with stimulus 2. Let me use a different color. So stimulus 2 Let's say that stimulus is stronger and that opens 8 sodium channels, so I'll do that over here. So we open 1,2,3,4,5,6,7,8. Now that goes a lot further, right? And that got me to about minus 62. I'm still not at minus 60. So do you notice that they're dependent on the stimulus strength? The stronger the stimulus, they further they travel. All right. Well, now let's say that we're going to

have stimulus. We'll say stimulus 3. I'm going to use a highlighter here so you can see it. And let's say that that opens up 10 gates. So we're going to apply that stimulus here and notice we go 1,2,3,4,5 and I get all the way here and I opened up 10 channels because it was a stronger stimulus. Well, if I open up those ten channels and now it hits right there at minus 60, now boom, I get an action potential. So they're called graded because they're dependent on the stimulus strength. The stronge

r the stimulus, the more sodium channels open, the further along it travels if it reaches the axon hillock, where the voltage gated sodium channels are and it hits threshold there, then you get an action potential which is then going to shoot all the way down. So that's a graded potential. The other thing about graded potentials is they can either depolarize so they can make it right, depolarize, make it less negative, or they could actually hyperpolarize to see how they can hyperpolarize. Now w

henever we're depolarizing, we're pretty much - there's one way to do that. And that's to open those sodium channels. Sodium enters and it becomes more positive, you can say less negative. When we want to hyperpolarize the neuron, see how we're making it more negative. Remember that we can open potassium channels and that potassium will always leave. And we said that would hyperpolarize it. So one way they do it is they open potassium channels and potassium leaves. There's another way they work

that they can do this, they can open chloride channels and there's always more chloride outside of the cell. So if you open a chloride channel, chloride is going to come in. So another recommended video is going to the big picture animations and viewing the local potentials because it does a really nice job of going over graded potentials. And again, I normally would throw it in the lecture, but I'm not. I'm not going to force you to watch it if you don't think it will help you. If you're strugg

ling at all, go watch it. It'll be very good. So now we need to talk about the action potential. So the action potential is once we reach threshold and that only happens in an axon. So it's just a propagated change. It means that once you hit that negative charge, it's going to go all the way through the axon until it gets down to the end to the axon terminals. These action potentials follow the all or none law. So if it's threshold, if it reaches the magic number of minus 60, then all the volta

ge gated sodium channels pop open and it just rushes into the cell and you get that wave of depolarization. If it's stronger, you get the same result. So in my previous example when I said, OK, well let's open up 10 channels, I would get the same result if I opened 20 because all I gotta do is get right here at minus 60 and the exact same thing happens every time. So that's why it's called the all or none law. It's you hit threshold, boom, you have the same action potential, the same intensity.

No matter how big the stimulus is. So you either have one or you don't. So basically we look at the top graph here. What we're looking at is we have our minus 70 at rest and then we get some sort of threshold that is going to cause the voltage to go up. Remember, that's called the depolarization. And then we need to repolarize. So there's basically four steps that happen for this to occur. So step one is I need to have a threshold stimulus. The threshold stimulus opens voltage gated sodium chann

els. So step one threshold stimulus opens the voltage gated sodium channels and sodium rushes in. So I flip the charge. I've depolarized my cell. Now remember that happens at, I don't care if you want to learn minus 55 or minus 60, depends on what book you're looking at. Now the second thing is that once we hit plus 30 mv, that's when the voltage gated sodium channels close. So now they close and they can't open. Notice they become inactive. The third thing that happens at plus 30mv is the volta

ge gated potassium channels open. Now remember, if you open potassium channels, potassium is going to rush out of that cell. So now we're losing positive charges and we repolarize, we start to come back down. Step 4 is that the voltage gated potassium channel start to close. Now you don't have to know the voltage that they do this, but I want you to know that when they start to close, they're very, very slow. And because they're slow, if potassium is all running and trying to get out of that cel

l, they start to slowly close and extra potassium scoots out. And that's why you'll notice there's a very brief hyperpolarization. See how it goes even more negative. Every time a neuron goes through this action potential, there's a brief hyperpolarization, and then the sodium potassium pump kicks in and it comes right back up to the resting membrane potential, and it's ready to do it again. Now, in your notes you'll also notice and you'll see on the graph that there's something called a refract

ory. So the refractory can be absolute or relative. So the refractory, generally speaking, it's just a time period that you can't send another action potential with the same stimulus basically. So it's basically once it returns to resting and the membrane doesn't respond the same. So there's two of these, there's an absolute and a relative. The absolute is "absolutely no way" you can get another action potential. Those sodium gates are either already open, so you're already getting it, or they'r

e closed, you can't open them. So we look on the graph and notice the absolute refractory. Is when the sodium channels are already open, right? Or they're closed and incapable. So you cannot generate another action potential. Relative is you know what, you can generate another one, but you need a stronger stimulus. So this is only when you have a larger stimulus. So if you look at the relative, notice the relative is when there's that hyperpolarization. So you would need a stronger stimulus. Bec

ause remember, let's use minus 60 as threshold to go from minus 70 to minus sixty took a change of 10 volts, right 10 millivolts. Let's say during this hyperpolarization that it's minus 80. Now you need a voltage change of 20 right millivolts, so you would need to open more sodium channels to hit threshold. So threshold does not change. What changes is the neuron is hyperpolarized, so it's now further away from threshold. So you need a stronger stimulus to depolarize it. Now you know the absolut

e refractory is pretty important for several reasons. One of the main reasons is remember that as these ions are rushing through, it's like this wave of electricity that shoots through the axon. And so when you were let me go to a picture of a of a neuron here. So if we were to look at a neuron. Clean this up a little bit and we were going to look at when it depolarized. So that sodium rushes in. Remember that it's going to rush in and rush in and it kind of spreads like an electric electrical w

ave across the cell. Remember that right behind it it's going to reset, potassium leaves so you can reset it. Well, the absolute refractory is very important because remember there's a time period that you can't conduct another action potential. And what that does is it forces it to move one girection only. It does not allow it to travel backwards because the whole thing is very electrically excitable. So that absolute refractory gives the neuron a chance, a brief rest. But it's critical because

it prevents the action potential from running backward. It forces it to go all the way down to the telodendria to those axon terminals that are at the end. So it's pretty important. Now I put a table in your notes that just kind of compares and contrasts graded potential with action potential. So remember that graded potentials always happen on the dendrites and the cell body where only the axon can generate action potentials. When we're looking at a graded potential, it's the chemically gated

and as well as the mechanically gated channels that are going to cause them where it's the voltage gated for the action potential. As far as the amount of the voltage change, just know this is fairly small where this is very, very big. Remember an action potential actually goes from minus 70 to plus 30, whereas the graded potential, it's only going to go to minus 60 because it needs to hit threshold. The all or none law does not apply. All or none law only applies to the action potential because

a graded potential is dependent on stimulus strength. The duration is very short. It's much shorter for the graded where the action potential goes all the way along the axon. The graded potential travels short distances, maybe from a dendrite to an axon, where the action potential goes the whole length of the axon and then changes in intensity. We know that this is going to decrease with distance and that this is going to stay the exact same because it follows the all or none law. Another thing

to keep in mind is that when we look at the voltage change, remember a graded potential can either be excitatory or inhibitory. It can be positive or it can depolarize or it can hyperpolarize. Whereas we look at an action potential, it always depolarizes and then it repolarizes. So it follows the exact same sequence or series as it goes through it. So I recommend that you watch some of those videos I showed you in this lecture because this can be a bit tricky. There's also an Interactive Physio

logy that goes over this that I think is really, really helpful. And then I have some things in the helpful links as well. So this concludes our lecture on the neurophysiology, the graded potential and the action potential.