Now a motor unit would be defined as the motor neuron and the skeletal muscle fibers that it innervates. So each motor neuron innervates more than just one muscle fiber and when you put them together that would be your motor unit. So when an action potential happens in the motor neuron, all of the muscle fibers within that unit are going to be stimulated to contract. Each muscle has more than one motor unit. so here you can see a single motor unit with where you have that one motor neuron supplying five more muscle fibers so this is when this muscle or when that neuron is stimulated it is going to lead to the contraction of five all five of these muscle fibers Here are two different motor units, again, motor unit orange and purple. So if you stimulate the orange motor neuron, that will lead to the contraction of the orange fibers only. The sizes vary among these motor units, so you'll find areas, for example, muscles of the back. Each motor neuron is going to innervate. thousands of muscle fibers because you do not need that fine movement of the back. But that is a little bit different when you talk about the small muscles of the hand or the muscle fibers in the eye. These motor units are smaller where each motor neuron might supply maybe only about 10 or 13 fibers because you need that very delicate and fine movements, whether you're talking about the small muscles of the hand or the eye muscles. okay in order to increase the contraction or the force of the tension produced in your muscle you the body has the ability to recruit more and more units so if you're trying to carry something the bodies are very conservative they will try to do it first with the smaller units and if it if they're unsuccessful they will start to recruit more units so you can gradually increase the tension that is produced by your muscles by again recruiting for first the smaller units and then gradually going up to recruiting bigger units and small so on now for the neuromuscular junction now how is it that the order goes from the nerve to the muscle Okay, we have these motor neurons that go to your skeletal muscles. Those are known as alpha motor neurons. You are going to find the cell bodies in the brainstem or in the spinal cord. They are myelinated, and they are going to carry the action potential all the way down to the muscle fiber. How would it get from the... motor neuron up here to the muscle fiber down there. That is known as your neuromuscular junction, where you have the nerve ending, okay, with these little vesicles. Those vesicles have acetylcholine in them. You have tons of mitochondria. That right here is a Schwann cell, so these are myelinated fibers. You have the synaptic cleft, and that's the gap between the nerve and the cell membrane or the sarcolemma. You can see these little folds, and these folds have the acetylcholine receptors. Just like we discussed this a couple of times already, but when the action potential reaches the end of the neuron, that will lead to the opening of calcium channels here. Calcium will rush into the neuron. That will lead to the activation of the SNARE proteins. Opening up. the vesicles leading to acetylcholine being released through exocytosis, they'll attach now to the acetylcholine receptors on the other side. And that is how we have, you know, you've transmitted the electricity from the nerve now to the muscle fiber. Okay, so that is, you know, we've talked about all of these neuromuscular junctions. The neurotransmitter of the neuromuscular junction is acetylcholine. That whole area where... that the part of the muscle fiber that actually meets the nerve is known as the motor end plate motor and point this is the whole story you could see the different you know the events as they occur so you have the motor neuron going down the or the action potential going down the motor neuron that will open up these voltage-gated calcium channels calcium enters it'll activate the snare proteins releasing acetylcholine via exocytosis acetylcholine will attach to the cholinergic receptors call it that will lead to the opening of the ligand gated sodium channel so sodium will start to enter if you reach a threshold potential of negative 55 inside of the muscle that will open up your voltage gated sodium channels and now you have led to you know an action potential that has initiated here in the muscle fiber All of the neuromuscular junctions in the skeletal muscles are excitatory, so any command coming from a motor neuron will lead to a muscle contraction. We'll find that that's a little bit different when you talk about the smooth muscle, for example. In order to get rid of the acetylcholine, you would do that through an enzyme known as acetylcholine esterase that'll break down acetylcholine and stop the neuromuscular transmission. So what are a couple of disruptions that can happen to the neuromuscular signaling? So there's curare, and that is usually used as a deadly arrowhead poison. It binds very strong to the acetylcholine receptors that are found at the neuromuscular junction. So if you block those receptors, that will prevent the ligand-gated ion channels from opening, and... it can lead to death okay because you are going to also one of the muscles that are going to be technically paralyzed in here would be your respiratory muscles including the diaphragm okay the disadvantage or one of i guess if you're hunting it would be considered an advantage is that it does not get destroyed by acetylcholine esterase so again you've technically you Curare is going to bind to those nicotinic cholinergic receptors and blocking acetylcholine from reaching them. Other things that can block the neuromuscular signaling would be organophosphates. These are found in pesticides. It's also known as nerve gases. These organophosphate inhibit acetylcholine esterase. So we are no longer going to break down acetylcholine. It will stay attached to the cholinergic receptors, and that is going to lead to too much contraction. An antidote for organophosphate would be pralidoxime. That is going to prevent the action of the pesticide and the nerve gas. You would also want to give something to open up, something to block the receptors, and that would be atropine. A third disruption would be succinylcholine, and you can see from the name that it is a relative of acetylcholine. It'll attach to the cholinergic receptors. It's higher in its affinity, so it'll attach to the cholinergic receptors and prevent acetylcholine from attaching to it. We use them to initiate some kind of muscle weakness. muscle paralysis before surgery or during surgery. The patient, though, has to be artificially ventilated just to make sure that, you know, because this will also affect the respiratory muscles. A toxin that is produced by a bacteria known as Clostridium botulinum that can block the release of acetylcholine, and I believe we talked about that before, when you block that When you block acetylcholine from being released, well, you no longer have that neurotransmitter, so there is no contraction that is going to happen. The botulism occurs due to breakdown of the proteins of the snare proteins. Okay, so again, acetylcholine is there, but because you've destroyed those snare proteins, it can no longer be released. We can use botulinum toxin in Botox injections. Okay, that's what we give. It can also be used in other things like severe migraines or in excessive sweat gland activities. Or we already talked about the Botox injections. Now, how does a muscle contract? And I want you guys to watch this to understand the contraction of the muscle fibers. So this right here. are your myosin fibers these are the myosin heads These are actin and these are the actin binding sites. So I'm not sure if you'll be able to hear what they're saying or not, but at least we can watch it together and I can narrate. So where the myosin head is attached to the actin binding site, that's known as a cross bridge because you bridged that gap between myosin and actin. And then you can see here that it will pull on the actin, kind of bending, and that is known as the sliding of the filaments. So you have actin sliding above myosin fibers. This is the actin filament to slide by. As you see here that the contraction or in order for the myosin head to let go of the actin binding site, it needs to get a molecule of ATP. So if there's no ATP, that myosin head will stay attached to the actin binding site and will not let go. When the head gets ATP and breaks it down into ATP and phosphate, it will take that energy and release. It will be into what is known as a cocked position, which means that it's pretty much ready to attach to the second binding site to perform a second crossbridge and more sliding of the filaments. This is what we're really talking about here, how the myosin head and actin interact together. This is talking about the structure of tropomyosin, which are basically the ropes that cover the actin binding sites. They are kept in their positions by troponin molecules. Now what happens is that when calcium comes in it will bind to troponin and troponin is going to change its shape. When it does so, now tropomyosin is able to expose the actin binding sites. Now myosin head will be able to attach to it and produce the muscle contraction that you've seen in that video. So when you want a muscle to relax, you really have to get rid of the acetylcholine, obviously in the neuromuscular junction. You also have to get rid of that calcium. Now where did that calcium come from? Remember that calcium was stored in the cisterns of the sarcoplasmic reticulum. So that action potential opened up these calcium gates, calcium comes out and performs its function. Now here you can see the action of the cross bridging where myosin head would like to attach to the actin but it cannot because troponin keeping tropomyosin in place and as you can see it is but it is hiding the binding sites this is under that's when a muscle is relaxed with low cytosolic calcium levels so notice I'm not saying low blood calcium levels I'm saying low cytosolic calcium levels so the calcium levels inside of the cytoplasm of the muscle is low now when an action potential comes and opens up the calcium gates Calcium will be released from the sarcoplasmic reticulum, increases in the cytosol, it will attach to troponin, and you can see here that now tropomyosin is moved and these binding sites are exposed. Now the myosin head is able to attach to them leading to that cross bridging. Now how do we increase the levels of the cytosolic levels of calcium and I will like to you know do a brief intro and then go to the slide that has the image. Remember we said calcium is stored inside of the sarcoplasmic reticulum and there's a gate. It's a voltage-gated calcium channel with two different receptors. One is known as DHP or the dihydropyridine and the other receptor is known as ryanodine. These voltage-gated calcium channels have two keys. Now when the action potential reaches the skeletal muscle, it will that is your t-tubule okay so you see how the action potential goes into the t-tubule that will lead to the activation of the voltage gated calcium channels through the activation of the dhp and the ryanodine receptors these are your two keys gate the calcium is released into the cytoplasm now that we have high calcium levels in the cytosol you It'll attach to troponin and start that cycle. In order to get rid of calcium, calcium would have to be pumped into or sucked back into the sarcoplasmic reticulum through an active pump known as the calcium ATP pump. So that, again, is an active pump that will vacuum calcium back into its storage, back into the sarcoplasmic reticulum, and that is a way to stop the muscle from contracting. So the sliding filament mechanism is where your myosin and actin slide on top of each other. We've seen that in the video. You want to make sure that you're familiar with what the sliding filament model means. Here you can see that when the muscle contracts, you can see here little gaps in between. but these gaps become shorter because of the sliding of the actin on top of myosin that leads to the shortening of the sarcomeres and that translates we are able to see that in the form of a muscle contraction this shows you the whole cycle you can watch the video you know on your own to kind of understand better understand how this works One of the parts that I want to get your attention to that we have not talked about is one thing that again in order for the head to let go of the binding site on actin it needs ATP. When it does that it will let go. okay, and be ready to attach to another binding site. But if the person is dead, okay, the person no longer has ATP, that means that relaxation is not going to occur. And that is why right after death, there is rigor mortis, which means that stiffness of the muscles due to the failure of these muscles to contract. because again that myosin head can no longer break down ATP and that it needs that ATP in order to let go of the binding site on actin so we've talked so many times about ATP and skeletal muscle contraction now let's kind of organize our thoughts on there. How many ATPs do we need? Where do we need them? So we need ATP at the sodium potassium ATPase pump in the plasma membrane. And that, remember, was part of the whole action potential process. Okay, we also need ATP to get rid of calcium. So there's the calcium ATPase in the sarcoplasmic reticulum to bring calcium back into its storage. We have to break down ATP at the myosin head. And we also, that energizes your cross-bridging. It is going to provide the energy for that force for the sliding of the filaments. And we also have to bind ATP to myosin in order to let go of the cross-bridges. These are the sequence of events on both slides and I'm going to let you folks go ahead and read them. We've talked about them all. There's nothing new in there. But if you have any questions about them, please reach out and let me know.