All right, folks. We're moving along here in our discussion of muscle cells and the contraction properties associated with muscle cells. We've been focusing on skeletal muscle, and in our last video, we talked about the contraction mechanism inside of the muscle cell, skeletal muscle cell, at least with the processes associated with actin and myosin.
In this video, we need to figure out how does a cell know when to contract? So, We're going to be talking about what's called the neuromuscular junction and the initiation of contraction. The neuromuscular junction and the initiation of contraction.
We have to get a signal over to the muscle cell to tell it to contract. So let's figure that out. In this first image here, I'm going to take you back a little bit. We talked about the action potential and nerve tissue and the propagation of that action potential down the... axon of a neuron.
And we spent, I believe that was in week four, that we kind of played with that. And I think it's important that you be able to bring that back because that's how we're initiating the contraction inside of the skeletal muscle cell. In this image, it's showing you a single, let me get my pointer out here for you, it's showing you a single muscle cell here. single skeletal muscle cell here.
You can see its membrane, you can see the sarcoplasmic reticulum in blue, the T-tubules in green, the myofibrils, and the myofilaments actually associated with this skeletal muscle. The one thing that we haven't talked about with this cell is this structure that's coming down and actually kind of communicating with it, the axon, the motor neuron. So this is the neuron sending its, the neuron that is sitting within the spinal cord, sending its axon out to a particular muscle, or in this case a muscle cell, to initiate contraction.
So I'm going to propose a little thought for you, or actually put this thought on your head already. Every skeletal muscle cell only gets one communication point, meaning only one neuron will come in and talk to him. All right, now, a neuron can talk to many different muscle cells if it wants to, but it's only going to get one spot where it can communicate with it.
And that spot where the axon of a neuron coming from the spinal cord over to the muscle cell, cell communicates with that muscle cell that's called the neuromuscular junction the neuromuscular junction in this image here over to your left here is a light microscopic image showing you muscle cells muscle fibers skeletal muscle fibers these are neuromuscular junctions that you see here this is a motor neuron extending down this one actually has branches and communicates with this motor neuron and this one but it only communicates on this motor neuron at this point and this new motor neuron at this point this motor neuron comes down and communicates with this one over here it doesn't communicate with the others they don't have another communication point so again these muscle cells are working independently And it's the job of the nervous system to find a way to get them to work together. Everybody understand that? We'll talk more about that in coming videos here, in coming videos.
Go back to our cartoonish image here. Over to your right in the circle, it's blowing up where that axon is synapsing onto the muscle cell. This, classically, is the neuromuscular junction.
So we have neuron extending down. We have the presynaptic area here where you can see inside of the synapse or, excuse me, inside of the presynaptic terminal where you can see the synaptic vesicles that'll hold the neurotransmitter. You can see the synaptic cleft.
That's the space that will be between the actual nerve cell and the postsynaptic side, which is whatever the effector cell is. And in this case, it's the muscle cell, the skeletal muscle cell. So this is the postsynaptic side, or postsynaptic membrane here.
Everybody got that? You can see in this skeletal muscle picture here also, here's a t-tubule. Remember us talking about that? This is the extension of the cell membrane deep into the cell, deep into the cell itself.
And inside of the cell you can also see the sarcoplasmic reticulum. Remember that from our last video? We're going to try to bring all these guys together here in a little bit.
So neuromuscular junction, presynaptic area, postsynaptic area, synaptic cleft. If you remember all of the pieces of a synapse, they're all here. So let's talk about this in a little bit more detail here. This neuromuscular junction, it is trying to maximize the amount of tissue or the amount of muscle cell membrane that is actually exposed to that presynaptic terminal. It's really pretty fascinating that you actually see these kind of folds that you'll see on the muscle cell side called subneural clefts.
These clefts actually help increase surface area. Does everyone understand what that term means? Increase.
surface area, meaning trying to increase the amount of surface that comes in contact with the outside world, I guess you could say. And in this case, by folding, we get to have more membrane exposed to what's going on or what's being released from the presynaptic terminal than if we just had it, you know, flush sitting across the end here. With more membrane, that means we can put more receptors, more channels, more... carriers and have a stronger effect, have a better effect.
In fact, in this next image, it shows you a little bit of that. Again, up at the top, this is the presynaptic terminal or the part of the neuron. These are the synaptic vesicles that have the neurotransmitter.
And when we're talking about the neuromuscular junction in mammals like us, we're talking about the neurotransmitter that's sitting in these vesicles being a very small part of the neuron. specific type acetylcholine acetylcholine acetylcholine is the main neurotransmitter at the neuromuscular junction of mammals like us okay all right the release of that neurotransmitter acetylcholine getting out into the cleft its job or it's the job of the postsynaptic side and the receptors the acetylcholine receptors to be looking to link to those acetylcholine molecules. If they bind to those acetylcholine molecules, they will open up channels and allow sodium into the muscle cell.
Now remember what would happen if we altered the permeability of sodium to the membrane of a neuron or any other cell? The cell would depolarize. It would become, it would generate an action potential.
Here in these muscle tissues, in these muscle cells, they do do the same thing. Sodium comes in, it will link up and change the, or excuse me, sodium will come in and change the voltage on the inside of the muscle cell. That voltage becomes more positive. There at the bottom of the cleft, you can see here, there are voltage sensitive sodium channels. When the channel or when the inside of the cell becomes a slightly more positive, it opens up all of these sodium gates down here and even more.
more sodium comes rushing in. We have a full-blown action potential taking place now. Everybody understand that?
So now we're pulling in that information about membrane voltages, channels, charges, and forces moving across the membrane, the action potential. And now we're moving it over to another tissue where we can actually initiate some other response. So now we need to take it to that level.
In this image, another slide just trying to show you pre- presynaptic area. So this is the presynaptic terminal. The axon would be coming down, and this is the end of the axon.
Here's the synaptic cleft and the postsynaptic membrane here. Acetylcholine receptors on the postsynaptic side. waiting for acetylcholine to be released. Once that acetylcholine is released, it'll bind to the receptors, setting off an action potential, which will propagate.
That's what these arrows are trying to show you. They're propagating away, propagating away from the initiation site here. Soon as acetylcholine is released and tries to get over and bind to receptors on the postsynaptic side, there's enzymes sitting within the cleft and in the membrane on the postsynaptic side, acetylcholine esterase that is ready to take it and break it down.
Why do we want to break it down? We don't want acetylcholine just sitting there all the time. We want, whenever it's released from the presynaptic side, to get over to the postsynaptic side to be a very discrete signal.
We need it to be a discrete signal. If acetylcholine is left in this area continuously, causing contraction the whole time, you... have a very serious problem. We will not be able to to control the actual contraction very well. We need control and that's what the nervous system is trying to do here.
So this is the beginning of the initiation of contraction. Just getting the signal from the nervous system over to the muscle cells themselves. Now, before we move into the muscle cell and see what happens with that action potential, I want you to remember some features here.
You've seen this slide before. I've used it before to try to get you to remember some of these anatomical parts of the muscle cell. Membrane. The T-tubules here in purple and in blue over here in the left image, the sarcoplasmic reticulum, the myofibrils and the myofilaments sitting on the inside. Got that?
Over to the right, same thing. Myofibrils, the sarcoplasmic reticulum, T-tubule and the membrane and the membrane here. You remember those pieces?
Good. Let's see if we can take those further. In this image, let's make sure again we understand where we're at. Up at the top, this edge here at the top is the cell membrane, the muscle cell membrane.
Now, it's not showing you the axon or the presynaptic terminal up here. We're just going to assume it's up here and that this is a spot where we can initiate an action potential by releasing acetylcholine. If we can initiate an action potential, that action potential will spread across the membrane.
Well, remember the T-tubules? Those T-tubules are extensions of the cell membrane. So that's membrane going down. The action potential will actually follow the T-tubules, go down deep into the cell, trying to change the voltage of the membrane.
Well, as it's doing that, there are proteins that are linked to the membrane of the T-tubule and the membrane of the sarcoplasmic reticulum here in blue. If that voltage change across the membrane makes it to... one of those proteins.
Those proteins will change shape, open up channels in the sarcoplasmic reticulum, and release calcium. Now, let's see if you remember what's happening inside of the cell when calcium is released. Can you think about that for a moment?
Because I'm going to run through it again with you. Calcium is released. Calcium will bind to troponin on the actin filament.
It'll bind to troponin once... troponin binds it it will move the blue tropomyosin molecule or protein that exposes active sites on the G actin if those active sites are exposed myosin as long as has ATP will link to those G actin proteins and once linking and using that ATP it will cock and move the actin filament and move the actin filament we have contraction we have contraction now as soon as calcium is being released if you look over here the sarcoplasmic reticulum will activate pumps to start pumping it back in to start pumping it back in so calcium is only out there for a very short period of time. A very short period of time.
So it's got to do what it's got to do, or troponin's got to do what it's got to do as fast as possible to get a particular contraction to occur. Okay? Now, the response of a muscle cell to one action potential being set off on the membrane, moving down the T-tubule and activating the release of calcium to get muscle contraction to occur, and then that calcium being pulled back in, stopping the contraction, that is called a twitch.
Should we say that again? The response of the muscle cell to one action potential, one, one action potential, and that action potential being able to travel along the membrane, activating the release of calcium. calcium, setting off the contraction process, but then it getting pulled back in and then the process stopping, that is called a twitch.
That is a muscle twitch. Everybody got that? Let's go through this one more time.
In this image up at the top, you can see the neuromuscular junction. In some textbooks, older textbooks, you'll hear the motor end plate also used for this area. Neuromuscular junction.
presynaptic terminal, postsynaptic terminal, or the synaptic cleft in between. Acetylcholine is released, binds to receptors, sets off the action potential. The action potential propagates, is running along the membrane, running along the membrane.
As it runs along the membrane and comes to the T-tubule, it will follow the T-tubule down, down into the cell. As that action potential makes it into the cell. and changes the voltage across the membrane from positive outside to negative inside to positive inside negative outside, that will set off this protein or this series of proteins here in the middle called the DHP receptor.
We'll talk more about the DHP receptor here in a moment. When that action potential hits that DHP receptor, causes it to change shape, pulling the cork, allowing calcium to be released from the sarcoplasmic reticulum. Calcium links to troponin.
Troponin will move tropomyosin. Tropomyosin being moved will expose active sites. Myosin will bind and move, cock and move, the actin filament, shortening the sarcomere.
We have contraction. We have contraction. Everybody got that? We have contraction.
Thank you. In this image, DHP, that receptor, that protein, its full name, the dihydropyridine receptor. Dihydropyridine receptor.
The dihydropyridine receptor, again, much like I showed in the last image, when an action potential comes in contact with it, it's voltage sensitive. Voltage sensitive on the inside of the cell. So if it's positive on the inside, boom, pulls the cork, calcium is released. When it's repolarized or...
in the resting state, it's closed and calcium is stored and sequestered literally inside of the sarcoplasmic reticulum. Over to your right, another image trying to show you what people have characterized the DHP receptor to look like. And it's actually a complex of receptors.
So the DHP receptor is a protein that sits in the T-tubule while over in the wall of the sarcoplasmic reticulum, we have a... slightly different receptor called the rhinodyne receptor. These guys work together. to either keep calcium in or allow calcium to be released from the sarcoplasmic reticulum. The rhinodyne receptor is really quite interesting because this protein we actually find in the eyes and is important for how we perceive vision as well.
So very interesting how the body tries to conserve or reuse particular proteins in our body. In closing for this mini lecture, I wanted you to see and kind of relate the time frame for us to actually get a contraction to occur. Okay, because I'm sure you... can already feel that we've gone through multiple processes here to just try to get a single muscle cell to contract. A single muscle cell to contract.
So let's put the timeline together here. Down on the axis, on the lower axis, this is milliseconds. Zero, and the red line is when the action potential actually gets to the surface of the cell and releases acetylcholine, and releases acetylcholine. Everybody got that?
Once that happens, you would think everything is instantaneous. Well, milliseconds-wise, it takes time for the calcium to be released, that's the dotted line here, to get... into the cytoplasm so that troponin can actually link to it. So here's when calcium is released. Here's when it actually binds to troponin.
And remember, when it binds to troponin, it's moving tropomyosin so that we can start to get the contraction process to occur. Well, as soon as that occurs, then we get the twitch. This is the maximal force of that single twitch.
Remember, the contraction will only last as long as how long we have calcium available and ATP available. So you can see from this, this is the actual muscle contraction or twitch that's occurring. From the time...
that the action potential or signal gets to the surface of the cell to the time of the maximal contraction, that's 60 milliseconds. Now, I know that may not sound like a long time, but that's almost an eternity if you think about it. We think of our muscle movements being quite quick.
That actually takes a long time, 60 milliseconds. I want you to remember that because in our next few lectures, we're going to be talking about this delay that takes place because of all the processes we have to do to get this muscle to contract. We'll talk to you later.