So I want to kind of walk you through sequentially and just ask you to bear with me because there's some stuff that kind of needs to get said to make other things later on make a little bit more sense. So I believe this is page 90. Page 90 in the packet. It's getting warm in here.
So we've talked about membrane transport. We did that exercise a week ago. What we're eventually moving towards is talking about nerve signal transmission. Well, there's signal generation and transmission.
And how do these neurons create this electrical signal, like electricity moving through a wire, and how does that get transmitted to the next cell? And how does that end up going to your brain from a receptor and then from your brain back to an effector and so on? That's kind of where we're moving towards.
But it's all based on this concept of membrane potential. So we can define this as the charge difference between the extracellular fluid and the intracellular fluid. I'm just going to abbreviate that ICF.
or the cytoplasm. So that circle is a cell. Here's our extracellular fluid. Here's our intracellular fluid, our cytoplasm. And you can do this if you have the right equipment.
If we were to take a probe and put it in the extracellular fluid, and another probe and place it through the cell membrane inside the cell and then connect both of these to a voltage meter. There's our little needle. I can swing back and forth there. We would notice that there is a difference in charge on either side of the membrane. And when we look at the voltage meter, what we would find is that the charge on the inside of the cell would be more negative than the charge on the outside of the cell.
Doesn't mean Well, I'll call this back out here difference We're so basically what this number is that the voltage meter is going to give us a value and then the cell it's going to be measured in millivolts That value is simply the difference in charge So it's a relative Charge it's not an actual 120 volts like coming out of your wall. It's simply the difference in charge between two locations Now a couple of points here. That cell membrane, the phospholipid bilayer, acts as a voltage separator or charge separator.
That's a better word. And when I talk about charge, what am I talking about based on those videos you watch? What are we keeping separate on either side of that membrane? Sodium, potassium, what do we call those? Ions.
All right, so that charge side, that cell membrane is keeping these ions, the sodium and potassium and chloride ions, and there's... ions inside the cell, anions inside the cell, it's keeping those all separate from each other in certain ways. And that's important.
Now this membrane voltage or membrane potential as it's called, this difference in charge can be measured anywhere from negative 60 to negative 90 millivolts. Different cells have, based on their function, different classifications of cells are going to have different voltages. And I'm going to call this a resting voltage or a resting membrane potential.
Now, a really important point is if you were to see a number, a value. That charge, whether it's positive or negative, is basically the charge difference based on the inside of the cell. So if the value is negative 70 millivolts, it means that the inside of the cell is 70 millivolts more negative than the outside of the cell.
It's always in reference to the inside of the cell. If it was positive 30 millivolts, it means that the inside of the cell is positive 30 millivolts more more 30 millivolts more positive than the outside of the cell okay so it doesn't mean the outside of the cell is going to be negative per se it's that that difference in those ions and the way they're distributed makes the inside of the cell more positive or more negative i see hand go up okay You can look at it that way, but it doesn't actually necessarily work that way, because we're looking at the difference in those concentrations. You just can't add up all the ions and say we have more positive ones here and more negative ones here. It's partially like that, but it's also based on the actual concentration and moles.
There's a whole separate equation called the Nernst equation, which I am not going to require you to know, and the Goldman-Hodgman-Fax equation, which helps us. to actually determine that membrane voltage. And it is considering all that stuff. It's considering temperature and the gas constant.
It's this huge formula. But yes, it's kind of like that based on these charge distributions and where things are located with respect to that membrane. So a couple of abbreviations you're going to want to make sure that you know. V sub M or RMP, they're kind of used interchangeably, but RMP or resting membrane potential would be the cell at its normal state when it's not stimulated.
And we'll talk about what happens when we stimulate a cell and how that can change the membrane voltage. So the VM or the membrane potential is this difference in charge and there is a resting value. Neurons on average about negative 70 millivolts. That's their resting membrane potential. Skeletal muscle about negative 90 millivolts, negative 85 somewhere in there.
I see all kinds of different numbers in the literature, but the value that we get is kind of an average of many measurements on many individual cells. All cells have a membrane potential, but excitable cells like neurons, muscle cells, cardiac. smooth and skeletal and there is some sensory epithelia so taste buds in the tongue um rods and cones in the eye um the organ of cordy the semicircular canals in there those hair cells When those certain receptors are stimulated, they trigger changes in that membrane potential, their own membrane potential, which then causes them to change their behavior.
Previously, we addressed cells changing their behavior when they're stimulated by a receptor of some sort. What we're going to find is that there are receptors on cells that can then trigger changes in behavior and the movement of ions. Most of those cells are neurons or skeletal muscle cells, but there are some exceptions. So that purpose then of the cell, I guess I already talked about that.
So the purpose of the cell membrane, as I said, is to act as a charge separator. I thought that said something else. I know I'm all over the place on here, so at some point you're probably going to want to maybe redo this, revisit this, create an outline of some sort, draw your own pictures, whatever the case is. Muscle cells, so skeletal muscle, cardiac muscle, and smooth muscles, they are actually able to change their membrane voltage.
And as a result of that change in membrane voltage... that then triggers something else happening itself. So I address that. Questions? Take a minute.
Look at these notes. Look at what we just kind of talked about. We're kind of really just defining this.
We haven't even talked about ion placement yet. Any questions arise? So let's then move to talk about why there's a membrane potential.
How does it get created essentially? How does it happen? So there's several factors that contribute to this resting membrane potential or this membrane voltage.
The first thing is that the concentration of ions in the cytoplasm of the cell does not equal the concentration of those ions in the extracellular fluid. So those little brackets represent the word concentration. So the concentration of the ions inside the cell are not equal to the concentrations of the ions outside the cell. And I know one of those videos, both probably, talked about the two different forces that are playing a role in determining the position of these ions and where they're found on either side of the membrane.
So what would be the first force that is determining where these ions are going to be? So we have a concentration gradient simply based on the concentration of the ions on either side of the membrane. If you imagine a cell with nothing in it, that eventually things are going to kind of move into the cell to a point where we have these concentration differences.
So we have a concentration gradient. And what's the other one? So we're talking about how...
We get to the point of having this membrane potential and how how these ions are just why these ions are distributed the way they are. Those are all part of it. So the what did you say?
So the electrical gradient. And I want to say that last Thursday, you guys, that was kind of what you had on there, right? That we have so electrochemicals simply the combination of the electrical, the charge difference in these ions, whether they're positive or negative, and the concentration gradient.
That's a combination of both. So concentration gradient is based on the concentration in millimoles, okay, chemistry term. And electrical gradients are based on charge. differences or charge of the ions. And what we see, and the videos talked about this, is that typically these forces kind of work together in that they can offset each other.
or and or add together Now I have the benefit of being able to erase my screen and putting more room in. I know you don't on your paper, so you might need an extra sheet or something. And you're really going to want to go through and reorganize all these, probably this weekend, and think about it and try and put all these pieces together and go back and do some more, reread some things. Okay.
All right. Well, let's kind of put this into play as far as a... cell is concerned.
So let's draw a cell. I'm just going to draw a square. And we already know that based on the charge distribution, based on the way the ions are distributed, is that the outside of the cell is more positive than the inside or the inside is more negative than the outside. And I didn't put it on the previous couple slides.
But we can call the fact that there is this charge difference, we can call this membrane polarity, like the poles of a magnet. You have a positive pole and a negative pole. Tell me once again if we were actually to have a value, what does that mean, that negative 70 millivolts?
Yeah, go ahead. It's 70 millivolts less. You said percent. Yeah.
That makes a difference. It's 70 millivolts less charged than the outside, okay? And that's key is that whenever we see this, it's always about the charge on the inside. Because what we'll see going forward is that these polarities reverse. And then at certain points, the inside becomes more positive than the outside.
And what we'll see is that... The inside will have this. That polarity will reverse and then it will actually go back to what it started again.
Now you've probably heard the term action potential. That's the whole premise of an action potential is this quick reversal of polarity and then reverse, re-reversal going back to that resting voltage and that's due to ion movement. So let's talk about the ions then. What were the three major ions, well four I guess, that we have to consider when talking about resting membrane potential?
Sodium, potassium, chloride. Now, calcium, I'm going to put it on here. We're not really going to talk much about it. And then we have what we call these large anions.
An anion is a negatively charged molecule or ion of some sort. So what we have inside the cell are these very, very large anions, which would include proteins, phosphates, acids, these organic molecules. And they're... pretty large and so they can't pass through the membrane and they basically have to stay inside the cell.
So these are impermeable to the membrane and it's these anions here that are going to determine the position of the other ion. And this is where the idea of concentration gradients and electrical gradients come in. So what we're going to find at the end of the day that the outside of the cell has a very large concentration of sodium compared to the inside. I'm just going to write it in smaller letters.
So the outside of the cell has a much greater concentration of sodium than inside the cell. And then inside the cell, we have a much higher concentration of potassium than outside the cell. And then we also have a larger concentration of chloride ions outside the cell than inside.
And if we want to talk about calcium, yeah, there's a lot more calcium outside than inside the cell. Now what we're seeing here is basically the final distribution of these ions after all is said and done. This is what we have. Now if we look at these and we go back and think about, I guess I deleted it, those gradients, the concentration gradient and electrical gradient. Let's look at sodium first.
Where is the sodium concentration gradient? If given the opportunity to cross the membrane, where would sodium go? It would go where? Into the cell.
It's more highly concentrated outside than inside. So given the opportunity to pass through the membrane, which it typically can't on its own, it would go into the cell. So let's use the green arrow to represent the concentration gradients.
So that's the sodium concentration gradient. Where is the potassium concentration gradient? It's to the outside, meaning potassium would leave the cell, given the opportunity. And then the chloride gradient. to the inside and same with calcium.
I'm not going to put it on there because we don't really talk about the role. In fact, we don't really even talk about the chloride role. We do address a little bit in the skeletal muscle.
But so that's our concentration gradient. But remember, there's also the electrical gradients. I'll use blue.
Okay, so So let's look at sodium. If we talk about electrical gradients, remember we're talking about positive or negative charges in this electrostatic attraction. I was always amazed as a kid when my uncles would take a balloon and rub it on their head and stick it on the wall. Oh my god, magic.
It's just static electricity. Your house gets dry in the winter, you have wool socks on, you rub them on the carpet, and you go up to your brother and you touch his nose and he gets shocked. Okay, static electricity.
Positives and negatives attract. That's an electrical gradient. So where is our electrical gradient here with sodium? Is there an electrical gradient, first off?
What is it? Where is it? There is an electrical gradient.
And the electrical gradient is what? Positives are going to be attracted to negative charges and vice versa. Like ionic bonding, in a way. Go ahead.
It'll also go inside. So the electrochemical gradient for sodium is that given the opportunity, sodium will cross the membrane because of its concentration gradient, because there's less sodium inside, and because the positive sodium is attracted to the negative anions. That's kind of a double redundant. The large anions inside the cell.
Now eventually what happens, as the video told you, is that it gets to the point where eventually the positive charges already in the cell will kind of repel some of the positive charges entering. And so what we get then ultimately is this more sodium on the outside than inside. That's what that results from, is that as sodium goes in, eventually it reaches a point where it's going to repel and push.
some of those sodiums back out because there's too much positive charge on the inside. Two positive poles of a magnet are not going to stick together. They're going to repel, and that's the same idea here.
All right, what about potassium? Where's the electrical gradient for potassium? Into the cell, okay?
In fact, it's a very, very strong electrical gradient. I'm drawing it with a much larger arrow. So the affinity of potassium for that electrical gradient is pretty high.
And just like with sodium, eventually, as the amount of potassium builds up in the cell, because of that positive-negative attraction, eventually there's too many positives, and that's going to repel and push some of those potassiums back out. Ultimately resulting in this distribution with potassium concentrated inside, more inside than outside. We don't really discuss it much, but since we're talking about it, let's do it. What about the chloride?
Yeah. Correct. So if we were to look at why would potassium go into the cell from the outside, it's because of this electrostatic attraction.
If there was more potassium on the outside than the inside, well, you would have two gradients, but those anions play a big role in keeping more of the potassium inside the cell than outside. If we were to look at chloride ions, where's that electrical gradient? outside.
The negative anions are going to repel the negative chlorides and that's going to result in more of those chlorides on the outsides. Now these concentration differences are going to be important when we talk about changing the cell behavior and muscle contraction and nerve signals because under certain conditions those ions will then move down those gradients. Sodium will move down both its electrical and chemical gradient.
Potassium can, even though it's attracted to the anions inside the cell, given the opportunity, it can still flow down. its gradient. So we can make a note here is that this membrane voltage establishes itself passively or naturally because of those very large anions inside the cell. Talk briefly about how these ions cross the membrane. So we know that at rest...
Ions are distributed a certain way. I'm going to erase that at rest there. Sorry. What I haven't mentioned yet is that there exist in the membrane things that we call leak channels. Think of a hose that's got a tiny little hole in it and you're getting just a little bit of water coming out of the hose when it's on.
It's a leak. So in the membrane there's leak channels and there's potassium leak channels and there's sodium leak channels. These leak channels are always open. So if we have these leak channels that are always open, what should that tell you about what's happening?
All the sensitive solutions. It means that there's going to be movement of ions across the membrane, right? Now before you get all... The actual amount of ions that move through these leak channels is minuscule. Very, very small.
Like if you were to compare it to a dripping faucet, maybe it's one drip every 10 minutes or something. It's a very, very, very small amount of ions. So what this means then is that we're going to have potassium leaking out of the cell because it's moving down its gradient, concentration gradient. Just because it has that electrical attraction to the anion doesn't mean it can't leave the cell. It does.
So we're going to have a little bit of potassium leaking out of the cell. Where's sodium going to go? So we're going to have sodium entering the cell. But again, this is a miniscule amount, but it's a natural part of the process.
But here's the problem. Well, you tell me what would be the problem over time if we just let these continue, even if it's a slow drip. What's the problem that we would eventually encounter if we just let these things diffuse?
So right, they can't leave through those channels. What else? Claire, what? We're changing the concentration of those ions inside and out of the cell, which could in turn change that membrane voltage, which we don't necessarily want. because cells have to be at that resting voltage prior to being stimulated to do something.
Like neurons have to be at negative 70, roughly somewhere in there. Reasons why they have to be at a certain voltage will become apparent Tuesday. So we don't want... We want to maintain that concentration gradient.
We want to make sure we always have more sodium on the outside, more potassium on the inside, and that that membrane voltage is as close as it can be or should be to what we're determining or calling its resting voltage. I've never found one. It's just one of those evolutionary things, and I'm sure there's research out there on those. These sodium channels were kind of first discovered in the late 90s, early 2000s. Some research indicates that they're important in the heart.
For heart muscle, you've heard that long QT syndrome, where these young, apparently healthy kids die in gym class because of an unknown heart issue. There's something called long QT syndrome, which means that the time that it goes from the Q wave of the EKG to the T wave is a lot longer than it should be. And there's research that seems to point that that may be an issue with sodium channels, sodium leak channels.
I haven't read any further than that. So the next question becomes then, well, how do we maintain this voltage even when we get these ions crossing the membrane through these leak channels? We have to maintain that. We want to maintain. a stable membrane voltage.
That's the goal. So what can we use or what can be done then to make sure that the concentration gradients remain the same and that the membrane voltage then stays what it should be because the ions are distributed correctly. We talked about this a week ago, the sodium potassium pump. So this remember is a form of primary active transport. It requires ATP directly to power that pump.
What? Primary. Like one degree.
That stands for primary. So if this is our sodium potassium pump, We obviously have to redistribute these ions. So which direction is the pump going to move these ions? I mean, think about why we have to have ATP involved in this. They're moving against their gradient.
It's counter transport going against the gradient. So what should be coming into the cell from the extracellular fluid? Potassium. Because potassium is flowing out through the leak channels, we got to bring it back in. And what should be leaving the cell?
Sodium. Anybody remember the ratio at which this pump moves sodium and potassium? Three what to what?
Three sodium, two potassium. So some cells expend upwards of 30 to 50 percent of their energy just powering these pumps. You will see questions, written questions or short answer fill in the blank type question.
Probably this one's going to have a little bit more short answer in that a couple sentences. per question. This next one.
I ask you a lot of questions about the stuff we just talked about, ion distribution and the sodium potassium pump and leak channels and stuff like that. Let's take a look at this picture here. So this is kind of where we're going to go with all this stuff in the remaining parts of chapter six. So we can say that A on this diagram is some type of sensory receptor.
which I talk about a little bit in the pre-lab lecture that you have to do for this upcoming lab. Some of you already had it. So B would be a sensory neuron.
Specifically, what kind of sensory neuron based on its shape or based on its structure? What do we call that one? Huh?
So these little things by the B there are the dendrites, but that nerve as a whole that has that little process sticking off the axon with the cell body out like that. It's a unipolar sensory neuron. And remember, where do we find those cell bodies? What part of the spinal nerve?
The dorsal root ganglion of the spinal nerve, okay? And then D here, or C, would be the axon. D would be the axon terminals.
And then, obviously, the neurons in black there would be the inner neurons, either the spinal cord and or the brain. And then the orange ones would be the motor neurons. In this case, are these autonomic or somatic neurons? Did you go over the anatomy of the autonomic and somatic nervous systems in Biology 152? This would be autonomic because the autonomic pathways, when they leave the spinal cord, always have two neurons and they synapse at another ganglion.
I know it's not the right color. but somatic only has one neuron that leaves the spinal cord and the spinal. So let's, so what we're going to be doing is, you know, we've talked about membrane potential, but where we're going is we're going to be looking at. Oops.
How does that sensory receptor then interact with the sensory neuron? How does that sensory neuron then, okay, are they the dendrites of that sensory neuron? How do they then relay the signal from the sensory receptor to the axon? How does that axon then convey that information down to the axon terminals? And how do those axon terminals then communicate that with this next cell here, which we would call the postsynaptic cell?
That's where we're going with all this. So for homework, you're going to be reading about... what we call graded potentials.
That's how the sensory receptors communicate with the dendrites of the sensory neuron. You're going to be reading about action potentials. and how those action potentials then are conducted down an axon, and then what happens at the axon terminals, and how that signal then crosses the synapse and starts that signal again in the next cell, and that's synaptic transmission. We're going to look at all that.
And then over here, we'll call this F. We're going to look at autonomic physiology, specifically autonomic motor, not sensory. And then G here, we're going to look at...
The receptors. on the effectors and how it affects autonomic behavior, autonomic motor pathway, physiology, autonomic motor pathways. We're going to look at all that.
So the receptor stuff that we talked about on Tuesday, we're going to come back to that. in a fair amount of detail in G, and we're going to tie it to the autonomic nervous system. And you're going to need to make sure you can think about, well, if this receptor is activated, why do we get this particular sympathetic response?
If the heart rate goes up when it's stimulated by the sympathetic nervous system, why is this particular receptor involved and what's it doing to the cell to make the heart rate go up? That's a big part of what... we're going to do.
That's basically the plan the rest of the unit. And it all relates to action potentials and receptor physiology.