Gen AP Muscle Lec Pt 2

INSTRUCTOR: So today we’re going to pick up with reviewing I would like you to review the neuromuscular junction by rewatching that animation, knowing the steps that are listed there, one through four And now we’re going to pick up with that action potential that has been developed on the muscle cell membrane after those four steps occurred So we have sodium flowing into the muscle cell membrane, into the cytoplasm here, and it starts an action potential on the surface, and it’s heading away from this neuromuscular junction So then what happens is we need to get that action potential from the surface of the muscle cell down deep into the muscle where the myofibrils are located, those tiny little contracting units So the first step then is we have to take the muscle cell membrane, and we have these what are called invaginations, which is little tunnels of the muscle cell membrane where that action potential can go deep down into that So these tunnels for that to occur are called T-tubules So a T-tubule is a structure It’s just a tube– think of it, a tubule– passageway for the action potential to go deep down into the muscle cell membrane And there’s a special organelle It’s a smooth ER that we find in muscle cells It’s modified to store extra calcium because we need a lot of calcium for muscle contraction to occur So that blue structure there is called the sarcoplasmic reticulum, not endoplasmic reticulum It’s called sarcoplasmic reticulum, and it’s unique to muscle cells Again, stores calcium So the muscle cell membrane has the T-tubules bringing the action potential down, and then wrapped around these myofibrils inside the muscle cell are these SRs, these sarcoplasmic reticulum, and it stores calcium So there’s another voltage-gated protein, voltage sensitive– it’s not quite a channel per se, but it’s a special protein that changes shape, and it allows calcium out of the SR into the extracellular fluid– or into the sarcoplasm I mean So when this action potential comes down the T-tubule, there are these voltage-sensitive protein channels They change their shape They allow calcium to flood the cytoplasm of the muscle cell So they bathe this muscle cell We call this excitation-contraction coupling when we take an action potential and link it to actual muscle contractions So we’re going to follow this whole process Again, it’s best to look at it in the animation to see things in motion, but let’s talk about some more structure So we have the T-tubule, which is a passageway for the action potentials, just an indenting of the muscle cell membrane And then we have the SR, and then we have these– the swelling here is a lateral sac it’s called It’s a collecting spot for calcium, because see how it narrows here? But where there’s a T-tubule, this SR widens, and we call it a terminal cisterna of the SR Terminal means the end of it, or a lateral sac, these swellings of the SR near the T-tubule So together, the two terminal cisternae and the T-tubule, we call a triad There’s three things involved– two terminal cisternae of the SR and a T-tubule in the middle A triad So that arrangement is critical for getting this calcium, extra calcium, released into the muscle cell membrane So we’re going to pick up with that So T-tubules, two lateral sacs, we call a triad And then there’s special voltage-sensitive proteins that serve as calcium channels if an action potential is present So calcium is critical for exciting the membrane and then releasing and binding the myofilaments, actin and myosin, which we’re going to get into here So let’s go to our animation here, which is in our Blackboard folder, in the lecture folder, and we’re looking at– got to find the right one There’s a lot of really good ones out there This one here So this worksheet–

I’m not sure if this page number is accurate anymore You might need to look around to find this actual picture in the latest edition of our textbook, but this is inside the muscle cell This is a myofibril What it’s made of, repeating units So we have myosin, the thick filament, the pink Actin is the thin blue filaments And those are going to interact in order to shorten this muscle cell So this is called a Z disk here, this structure, and this is called a Z disk here So the space between this actin myofilament and this actin myofilament where there’s no actin, this is called the H zone So down here, this is called the H zone, this arrow The space here is the H zone And then the area that contains the thick filament myosin, so from here to here, we call this the A band So from this arrow here to here, this space is called the A band, and it’s usually darker in color when we look at a slide of muscle because of the thick myosin myofilament It just picks up more stain and it gives it a darker appearance Can you see that in this actual photo how dark it is? It’s because of the thick myosin protein that is picking up more stain Can you see the little light area here? This is where the H zone is located where there’s no actin myofilament So it’s really dark here because there’s some actin and myosin overlap There’s more protein, picks up more stain, so it looks really dark here So this region here where it’s lighter in color is where we only see the thin actin filament And then another protein that ties myosin to the muscle cell membrane, this little coiled spring, is called titin T-I-T-I-N. That’s a protein that attaches myosin to the myofibril And what attaches actin to the myofibril is this Z disk protein So the yellow little springs– I’m using my arrow here The yellow little springs are titin, the blue is actin, and the pink is myosin This region from here to here is called the A band, and this region from here to here is called the I band And the same thing on the other side This is called the I band on this side, and notice that it’s lighter in color here, the I band So when you think of the word I band, where does that come from? Think of light The word light, for light in color, contains the letter I And the A band is found in the word dark A for dark So dark A band, light I band So when you’re looking at muscle tissue, you can identify that And then this dark line going down the middle of the I band is the Z disk So you can label that as well in the– so I want you to label it in the diagram as well as the muscle tissue That’s the Z disk A lot of terms today OK So what happens is– what we’re going to find is myosin attaches to actin and pulls the actin toward the center on either side of this M line This line here in the center is called the M line, and that too attaches myosin to the myofibril So we’re going to watch how this actin and myosin interact This is a relaxed muscle on the top, and this is a contracted muscle on the bottom So we’re going to go to our– I’m going to show you which animation you want to look at It’s the sarcomere contraction animation So I want to click on that and go over the parts And we’ll do that together, or you’ll do that on your own online The distance from one Z disk to the next Z disk is a sarcomere so that this whole thing here from this field goal to this field goal, Z disk to Z disk, is a sarcomere And that’s the structural and functional unit of muscle cell That’s what contracts and actually shortens in the muscle, and we’re going to witness that when you watch this animation here So after watching this animation and identifying what shortens and what doesn’t, we can go back to our worksheet and look at the first one What structures form the A band? Just put an X is all you have to do, or a checkmark The entire myosin myofilament, is that found in the A band?

The entire myosin myofilament? Yes or no? Yes Here’s myosin, the whole thing, and this is the A band Is it not? This whole thing is A band, so yes The entire actin myofilament, we find the entire actin myofilament in the A band? No We only find half of it Just a little bit is in the A band, so we’re not going to check that one The overlapping regions of actin and myosin, is that in the A band? Yes So we put a checkmark on that Only a portion of myosin that does not overlap with actin? Is that correct? Only a portion of myosin? No The A band contains the entire myosin myofilaments We’re not going to do that Half of each myosin that does not overlap, so that would be this half, is this found in the A band? No The protein that anchors the actin myofilaments to the myofibril, and that’s here, do we find– is that in the A band? No So how many did you check in number two? Two things– the entire myosin and the overlapping regions of actin and myosin Everybody agree with that? Questions? All right What structures form the I band? So we’re looking at this region here The entire myosin myofilament? No Nope The entire actin myofilament? Is the entire actin myofilament in the I band? Yes or no? No, because part of it’s here in the A band, so that can’t be the entire one The overlapping regions of actin and myosin, do we find that in the I band? Do we find myosin here? Nope Only a portion of myosin? There’s no myosin in the I band Correct? This is the I band right here We already labeled this There’s no pink myosin over here OK Half of each actin myofilament that does not overlap with myosin? Yes or no? Yes Yeah, because here’s half of the actin right here It’s in this region The protein that anchors the actin myofilaments to the myofibril, here, do we see this in the I band? Yes, so we would check that one So how many do we check in this one, and which ones do we check? We checked this one and this one Correct? The last two? OK So what structures form the H zone? Remember the H zone is this region right here What do we see? The entire myosin myofilament, is the entire thing in the H zone? No The entire actin? Definitely not The overlapping regions of actin and myosin? No A portion of myosin that does not overlap with actin? Yes Yeah Half of each actin myofilament? No There’s no actin in the H zone The protein that anchors the actin to the myofibril? No So what do we check? Just one This one here Only a portion of myosin that does not overlap with actin What structure contains myomesin, a protein that holds adjacent myosin myofilaments together? What do we call that structure right here? Did you label that? The M line Yep, the M line Make sure you label that on your diagram if you missed that What proteins help the muscle cell spring back to shape after contraction? Well, it helps you because they actually look like a little spring So as they are pulled toward the center, they bounce back and allow your muscle to relax again What are those structures called? Do you remember? Titin Yep T-I-T-I-N. So you can circle these on the diagram I would circle them here They’re a little easier to see The yellow springs, that’s titin And what specific structures make up the large, wide striations that we see in skeletal and cardiac muscle tissue? So these large, wide striations, what structures make up that? What? Yup So what structures do we find in the A band? What? Myosin and part of actin

So actin and myosin together, where they overlap is where we see that dark striations So actin and myosin for seven And number eight– and then also another thing, these dark structures here, what is that? Z disk Yep Z disk So actin, myosin, and the Z disks OK Next question is which zone or band disappears when the muscle is fully contracted? Right The H zone Which zone or band does not change in length during muscle contraction? Yeah, the A band stays the same, doesn’t it, if I look here? Which zone– OK What is the structural and functional unit of muscle which actively shortens during muscle contraction? Sarcomere Very good Sarcomere So this really helps us see the big picture We’re going to zero in now, go back to our PowerPoint– oops, not there Not there either Where am I at? I’ve got to find where we’re at now I’m lost OK So now we’re going to look at specifically actin and myosin and see what’s going on microscopically to allow them to interact and shorten a muscle So actin myofilaments have a couple of different things They’re made up of repeating units we call F actin and G actin So I’m on page 308 So F actin is a strand of 200 G actin molecules So what we see here, these are called actin, these are called G actin Each individual one is G actin If I look at a strand of 200 of these, collectively we call that F actin So I have a pearl necklace, the whole necklace would be F actin Each individual pearl, we call G actin OK So there is a strand– and this is all proteins They’re all little protein units So there’s a rope-like protein that covers the binding sites, because see, there’s a binding site here on each G actin And it’s a special binding site for another protein called troponin that binds calcium So there’s a rope-like structure called tropomyosin that covers these binding sites that make actin unable to interact with myosin if tropomyosin is covering those binding sites So there’s a binding site for calcium on this other protein called troponin So troponin binds to G actin as well as calcium So there’s a couple of different binding sites going on here And then there’s this tropomyosin that covers– see how it’s covering all those binding sites for myosin? So troponin is the boss that allows tropomyosin– it interacts with tropomyosin to move it out of the way so those exposed binding sites for myosin can bind to actin So tropomyosin is rope-like, and again, its function is to cover the binding sites for myosin So troponin, this little yellow structure, has three binding sites One, it binds to actin, two, it binds to tropomyosin, and three, it binds to calcium And we’re going to see how this all comes together STUDENT: [INAUDIBLE] INSTRUCTOR: Definitely Yes Yep STUDENT: Say there was maybe trauma that occurred to– INSTRUCTOR: The arm STUDENT: –skeletal muscle INSTRUCTOR: Yeah STUDENT: There was also concern of [INAUDIBLE] INSTRUCTOR: For the heart? STUDENT: [INAUDIBLE] INSTRUCTOR: Yeah STUDENT: You wouldn’t be able to use troponin fast enough [INAUDIBLE] INSTRUCTOR: There are cardiac-specific troponins that we look for Yes, because very commonly people can be in a car accident

as a result of a heart attack behind the wheel So now you’ve got a whole host of things in the blood Yeah Exactly So we have cardiac-specific enzymes that we can test for Good question OK So we’re going to watch an animation here of how we get myosin to interact with actin So if I look at a myosin myofilament, it has a binding site for ATP, and it has a binding site for actin So there’s two binding sites on this thick filament called myosin One is ATP, one is for binding to actin So it kind of looks like a golf club, and this is the part that can move This head, the myosin head, can switch back with the help of ATP It cocks forward and then pulls actin to the center to remove that H zone So we’re going to go back to the animations here and make sure that you know where to look to find this information And that’s the cross bridge cycle animation, so make sure you click on this and review this before you proceed with the next part of the PowerPoint So returning back to our PowerPoint, which I always seem to struggle and lose my spot Where are we at here? Where did my slides go? Did I kick them out? Here we go OK So after watching that video, then you should understand that calcium– looking at the events, is calcium binds to troponin, and when calcium binds to troponin, it moves tropomyosin out of the way and exposes the binding sites And as long as myosin has been charged with– what molecule charges the head and gets it ready to bind? ATP So ATP binds to myosin and then allows it to attach for a contraction to begin So as the actin is moving toward the center of the sarcomere reducing that H zone, that’s contraction So these steps is something that you should be able to list without looking to really understand this So we have to have ATP binding to myosin prior to binding myosin to actin, because what released actin and myosin from each other at the end? If you watch the video, you’ll see that another ATP had to bind to myosin and that detached it So as long as you have ATP available, it’s going to help cock the myosin head, pull it to the center, and then another one binds to make it release So when we talk about rigor mortis at death, that’s when we have a flood of calcium– the SR starts to break down We have a flood of calcium after death, binds to all those myosin heads– I mean, I’m sorry, binds to the troponin, and as long as ATP was originally available– which it will be for a short time until it’s not produced anymore because of death and lack of oxygen So what happens is that ATP binds, causes contraction, but there’s no more ATP to release those myosin heads from the actin So we call that rigor mortis, and that lasts for about two to three hours after death So it doesn’t last very long And there was a murder in our community a couple of years ago A guy shot his parents because he wanted money, and they stopped giving him money, and he said– the shooting happened on Friday He said he came to see them on Sunday, and he touched his dad, and he said he was cold and stiff And that’s impossible to be cold and stiff that far after death because rigor mortis doesn’t last that long STUDENT: [INAUDIBLE] INSTRUCTOR: ATP binding So if a person is dead, they’re not making anymore ATP, and then the muscle cell breaks down The proteins break down, and then they turn to– yeah Yeah So for a short time, we see the contraction occurring, but then after that, the proteins break down, and then they turn to mush Yeah Good question Yeah So we need ATP to bind, to release So at the end of contraction, another ATP binds, it causes the release, then that ATP splits and cocks the myosin head So here’s where it binds, cocks the myosin head back, and then the phosphate is released as it splits And that causes the strength of that myosin and actin

binding to be stronger, and then we have the power stroke And again, in order to release it, we need another ATP molecule So ATP plays a big role, and it’s all about binding to myosin That’s where the binding site is, is on the myosin head OK So again, understand what a myofibril is These are repeating units of actin and myosin filling that muscle cell So the muscle cell is full of these long fibers, of these myofibrils, and the distance from one Z disk to another Z disk we call the sarcomere And that’s what actively shortens in a muscle cell It’s the structural and functional unit of a muscle cell is the sarcomere That’s the buzz word for the muscular system The buzzword for the nervous system was neuron because that’s the structural and functional unit of nervous system It’s what the nervous system does It has a neuron that generates action potentials, while shortening of a muscle cell is accomplished by the sarcomere shortening So that’s the structural and functional unit, and that’s why it’s bolded and underlined So definitely important term for you to know So here, the sarcomere goes from Z disk to Z disk So as it’s contracted, you can see these two lines here get much closer together because it’s shortening We lost the H zone as we saw more and more of actin and myosin overlap So this and all these things here have the answers to that worksheet that we went through together in the earlier part of this discussion So cross bridge A cross bridge then is just actin and myosin bonded together It makes up a cross bridge So this just gives you a little bit more detail about what ATP is doing So step one, we form the cross bridge as ADP– or I’m sorry, as ATP splits to ADP and phosphate Then as those are released, that releases the energy and pulls the myosin head forward to pull actin toward the middle Then at the end of that, once that stroke is done, then another ATP has to bind to release actin and myosin, and then it splits again to cock that head to start the process again So how do we get muscles to relax? Well, we’ve got to cover up those binding sites on actin And what’s exposing the binding sites? Troponin binding to calcium Remember, that’s what pulled tropomyosin out of the way So if we take away the calcium, we take away the ability for actin and myosin to bond because there’s no more exposed binding site So calcium is actively transported back to the SR as long as there is no action potential available Because remember, what released calcium was the action potential coming down the T-tubule So if we get rid of the action potential, we get rid of the release of calcium from the SR, and then it’s just actively transported back to the SR and contraction stops So when calcium moves away from troponin and tropomyosin complex, those binding sites for actin are now covered, and we can no longer contract that muscle So again, we have to have ATP to bind to myosin to release that actin head If we have no ATP available, the muscle cannot relax, and we’re stuck in rigor mortis So how do we get stronger contraction then if we have this action potential and then we bind all of this calcium to troponin? Well, look at the number of muscle cells that are served by one motor neuron Let’s look at the motor neuron 1 So those axon terminals branch and serve three different muscle cells So the more muscle cells that are recruited to an activity, the stronger the contraction So again, it’s not an increase in action potential strength because it can only go up to plus 30 before those potassium channels open and it relaxes But it’s recruiting more muscle fibers So we have something called a motor unit So a motor unit is the same thing– I think I talked about this before If we did a tug of war in the front of the class, if I put 10 people on one side of the rope and put 2 on the other, the side with 10 is going to win because you have more people contributing to the force So the same thing with a motor unit Large motor units are motor units that have a lot of muscle cells for one motor neuron Your quadricep muscle has large motor units

Would you agree because it’s some of the strongest muscles in the body? How about your eyelid? Think there’s a lot of motor– think that motor unit has a lot of muscle fibers? Your eyelid? Probably not But the benefit of small motor units is they are better for more fine, precise, controlled activities Try drawing with your foot versus your hand You could probably draw– if I had to straighten my arm out and write my name on the board with a straight arm, smaller motor unit in my arm, the smaller motor units serving the arm than the lower leg Try to draw your name with your leg It’d be a little more difficult So fine, precise movements have smaller motor units So that’s the benefit of large versus small So it’s all about the number of muscle fibers contracting at the same time So delicate, fine movements, you just have a dozen muscle fibers in that motor unit So fewer motor units for fewer muscle cells in that motor unit So if we want to get maximum strength, we want all the muscle fibers in a motor unit contracting together And we can’t measure that in a lab because it takes extreme stress and duress to get all the motor units in a particular muscle stimulated For example, a mother sees her child trapped under a vehicle after it rolls over and they slide off the road There have been cases of women being able to lift a 1,000-pound vehicle or two-ton vehicle off their child How is that possible? It just shows that we have motor units that can be contracted together to give superhuman strength But you can’t simulate it in a lab because we’re not going to say, oh, I’m going to roll a car on your child and see if you can do it So we don’t know the true human muscle strength unless we have extreme stress So when we look at stimulating a muscle, a submaximal stimuli means some of the motor units are contracting in that bicep muscle, for example, if you’re going to lift something That’s a submaximal stimulus, so you have action potentials stimulating some of the motor units But maximal stimulus is when you have all the motor units contracting together Again, we can’t simulate that And if I stimulate more than the maximum number, that’s not going to help me If I took the entire class, and I had three on one side and I had the rest of you on the other side, you couldn’t pull with any more strength because I have everybody in the class working We couldn’t get a stronger force because we don’t have any more people It’s the same thing with our muscles We can stimulate a muscle like crazy, but if we’ve recruited all the motor units for that muscle, we’re not going to get a stronger stimulus So maximal stimulus means all the motor units are working in that muscle Submaximal means some of them are working For example, if I lift up this book versus a pencil, which one is going to have more motor units required? The heavier object The book OK So when we look at a muscle then, if I have a large number of motor fibers, again, that’s a larger motor unit If the fibers themselves are larger, that’s where strength training comes in If I’m a bodybuilder, and I’ve got a big bicep, that means my muscle fibers are larger So what are we going to have more of inside that muscle fiber? I can’t increase the number of muscle fibers, but what are those little units inside there? STUDENT: [INAUDIBLE] INSTRUCTOR: Well, zoom out a little bit Myofilaments in the myofibril Remember, the little tiny cylindrical unit within a muscle cell is a myofibril So the more myofibrils I have within a muscle cell, the stronger my contraction can be because I’m activating more sarcomeres So that’s what strength training does, is it just gives you larger muscle fibers And if I stimulate them constantly, I’m going to keep recruiting motor neurons with more motor units– I’m saying that wrong A motor unit is one motor neuron and all the muscle fibers it stimulates So if I recruit more motor units, I’m going to get a stronger contraction with a lot of action potentials going to my muscle cell and to multiple muscle cells and if I stretch it slightly beyond its resting length because I can get more actin that way Can’t I grab more actin if I pull those actin further out so I’ll have more actin heads to grab on to?

So if I’m going to lift something up, I don’t start midway through my lift If I want to lift something really heavy– look at a deadlifter Where do they hold that barbell? It’s all the way down They let it hang freely and then they lift the barbell So they stretch beyond the resting length of those arms, and then they lift it So if we slightly stretch it, we can grab more actin heads, or G actin filaments OK So where do we get the energy? With ATP But ATP can be quickly created in muscle cells by a special thing that we find in our muscles called creatine phosphate So we make creatine phosphate through anabolism, and it’s stored in our muscle cells And we can quickly get extra ATP by adding a phosphate onto creatine phosphate– I’m sorry, stealing a phosphate Sorry Stealing a phosphate from creatine phosphate, we can take ADP and make it into ATP very quickly So if I look at this, here’s creatine phosphate I have ADP, which is a used version of ATP, take that phosphate off with the help of creatine kinase, also found in muscle cells, now I’ve got ATP, and I’m ready to fuel that myosin head So that’s the first place to go to get more ATP is creatine phosphate Some bodybuilders actually will add this as a supplement to their diet You’ve probably heard of that So we’ll pick up on Wednesday talking a little bit about muscle contractions and just some more basic structures and things related to muscle cells in the next video