hey everybody professor along here professor Bob long junior anatomy and physiology lectures as everyone is aware the coab in nineteen coronavirus has everything shut down so I'm having to do these lectures and post them online so we're doing everything online these days this is muscle lecture five for my 2401 or human A&P one course so we've been covering muscle tissue we drew the structure of muscle from the muscle to the fastball to the muscle fiber to the myofibrils to the myofilaments we've done the molecular structure the myofilaments we've done the structure the sarcomere now we can put everything together we're going to learn how action potentials from neurons cause the release of neurotransmitters which bind to receptors on muscle cells which result in muscle contraction so before I get too far I want to review a little bit of what we previously cover so as you guys know the muscle is a bundle of fascicles there's a tendon down here at the end of the muscle inside the muscle or smaller structures called fascicles and the outer covering of the muscle is the epimysium if I fooled one fascicle mouth I would see that a fascicle Azam's covered with the same connective tissue covering as the muscle but around the fascicles called the perimysium and it is a bundle of smaller structures called muscle cells or myofibers now each muscle cell or myofiber is individually wrapped and surrounded by a connective tissue covering the same as the other team called the endo I see in the previous video I've pulled one muscle cell out a little bit so that we can see the cell membrane called the sarcolemma see that it's surrounded by these endomysium and then on inside of the muscle cell there's a bunch of smaller tubular structures long tubes of proteins called myofibrils and if you look at the muscle fiber models and lab they're a little bit more I'm just trying to draw a sort of representation of this if I pull one myofibril out throughout the myofibril there's these repeating subunits called sarcomeres we would have a Z line here like this with actin filaments sticking in this way and these repeating subunits I've drawn mine a little bit crooked but you get the idea would be interrupted by some other structures or in the middle of one of these sarcomeres so we have Z line here a Z line here and the Z line here I have to circle meters and then the addition of some portions of some other soccer music right down the sarcomeres are these played like proteins called M lines and sticking off the M lines would be my myosin filaments and you can see how they sort of interlock this way now last time we drew the molecular structure of actin and myosin then what we saw was these little myosin heads that combined to the active sites on actin and I have a whole bunch of G actin subunits here two rows of them with their active sites and as you recall from the last lecture which you should have watched the active sites are covered by another protein called tropomyosin and then there's troponin or troponin holding the tropomyosin over the active sites now there's some more detail I have not been able to give you yet and I'm going to give it to you in this lecture so you guys should be able to see all of this you should be familiar with some of this stuff and so what we're going to do is we're going to take this to the next step now one of the things I did last time is if you recall and this is really a parent from the myofibril model in the laboratory that model that has the yellow sarcoplasmic reticulum as you notice since the muscle cell is the cell that has a nucleus as a matter of fact skeletal muscle fibers being so long being filled with so many millions of protein skills have actually many many nuclei sometimes over 100 nuclei in one skeletal muscle cell so they're said to be multinucleate they also have all the same organelles or roughly the same organelles as other cells one of the organelles were used to talking about is called the endoplasmic reticulum or in skeletal muscle cells since it has some unique properties lots of extra calcium channels they called the sarcoplasmic reticulum and the sarcoplasmic reticulum is draped over and wrapped around the muscle cell like this and it's a series of interconnected tubules that I could see in between them so that I can see the actin and myosin lying underneath and the sarcoplasmic reticulum is broken up in a series of chunks that cover each sarcomere I'm not going to draw it quite anatomically correct the way that the model does in lab but I just want you to get the concept okay each tube you'll of the sarcoplasmic reticulum is called a cisterna a cistern is a large container that can hold fluids and each cisterna has a lot of fluid running through it filled with calcium ions it turns out the sarcoplasmic reticulum has a large calcium reservoir so it stores lots of calcium ions inside the cell and in between the sarcoplasmic reticulum if I look along the length of a muscle cell I'll see these little tubes that would run through the muscle cell called t tubules and then would be underneath the sarcoplasm underneath the end of my seam and broke it up here and so I'm going to draw a couple of t tubules running along here and this cell membrane would be continued now this myofibril has been enlarged it would be inside of our muscle cell but the cell membrane of the muscle cell the circle number would be cruising along like this okay now this cistern II that are budding or adjacent to the T mules are called terminal cisternae since this is the end of this chunk of sarcoplasmic reticulum and this is the end these are starting and running vertically here in my drawing next to the t tubules we called terminal so sternum and the structure called the Triad would be in terminal cisternae at each uvula in terminal cisternae then we would have a section of sarcoplasmic reticulum the terminal cisternae t-tubules terminal cisternae sarcoplasmic reticulum and it repeats at the night and infinitum all the way down the entire myofibril which runs the entire length of the muscle cell which runs the length of the fascicle and so on and every skeletal muscle cell in here what have the exact same structures and every minor fibro would be surrounding the sarcoplasmic reticulum in these repeating units now what I'm going to do is I'm going to take some of this and I'm going to magnify it a little bit I'm going to redraw and then we'll cut out here I'm gonna redraw this section a little bit bigger but I'm gonna start somewhere else first so our nervous system has our brain and our spinal cord coming down whenever you have the thought to move a part of your body the thought is initiated somewhere in the cerebral cortex and some neurons from the cerebral cortex will send information down they're going to synapse on another neuron that lives in the spinal cord and then that neuron is going to send on its axon all the way out now I'm going to start to enlarge this axon a little bit into two lines so we can see it and then that will fan out into some much smaller branches at the end of the axon and end up in these little boldness structures called synaptic noms I'm going to make one of the synaptic knobs much bigger than the others as a matter of fact I'm going to make one of these little branches bigger and a really large synaptic knob here this neuron that lives in the spinal cord is called a motor neuron and the reason it's called a motor neuron is because it results in motion some activity occurring when it fires now at the end of the neuron this long branch coming off the motor neuron is going to be referred to me as as - we're going to refer to it as the axon now we haven't done the neuron structure we haven't done a lot of neurobiology yet that's actually another two exams coming in the future but suffice it to say this long branch sticking from the spinal cord out towards our muscle cell is called the axon at the end of the axon if my arm were an excellent the exome is going to have multiple branches at the end that would have a little bulbous structure on the end each one of those little branches is called a tino vin Briand and i c3t load indriya here and each team of Gendry on ends up in a structure called a synaptic knob the synaptic knob it's called that because sometimes it looks like a doorknob it's also called the synaptic terminal a synaptic button and because some of this was described by some french fry french guy it can also be called a synaptic bouton but anyway it's the synaptic knob synaptic terminal we did the synaptic knob and I'm not going to do this for all of them all I'm going to do it for one there are small bubbles of membrane called synaptic vesicles now I'm not drawing everything this scale there would be literally thousands of these things much tinier but nonetheless every one of those little round structures in there is called a synaptic vesicle it's a little bubble of membrane that has a chemical in it called a neurotransmitter and the reason it's called the neurotransmitters because when I release that information that little molecule that chemical it's going to transmit a message from a muscle cell to a neuron I'm sorry from a neuron to a muscle cell when a neuron communicates to another cell whether it's a muscle cell or another neuron the chemical messenger that is released into a little gap that we're going to draw out here in a minute that's called a neurotransmitter so essentially neurotransmitters communicate information from a neuron to another cell in this case a muscle cell and I can draw add in some of these little molecules I'm going to just again nothing's to scale that would literally be thousands of these molecules in one synaptic vesical so one of the things I want to add here is that the synaptic vesicles are filled with the neurotransmitter and the neurotransmitter at the neuromuscular Junction we know for all animals whether it's us whether it's a deer or that or a cat or even in insects like roaches and bees and ants this we all use the same neural transmitter at a neuromuscular Junction and that neurotransmitter happens to be called acetyl choline which is abbreviated as capital a capital C and little H acetylcholine is the neurotransmitter released at our neuromuscular junctions you should know that you can learn this very very well better than you ever wanted to now once you know one synapse you pretty much know how all synapses work the only thing that will change is the name of the neurotransmitter the name of an enzyme that we're going to describe in a moment that can destroy the neurotransmitter break it down and the effects of the neurotransmitter at what's called the postsynaptic membrane so let me get to that so if I started to draw this cell membrane here it turns out that the cell membrane cruises along like this and wherever on their own neuron is gonna form a neuromuscular Junction the membrane gets a bunch of folds in it now one of the things that you should know from early in the semester is that any time we see folds in a membrane like with micro villi it increases the surface area and what this is going to do is increase the surface area of the circle ulema here of our muscle cell so that we can have an increased number and these little molecules these little proteins that are stuck in the cell membrane the more folds the more of these proteins they're integral membrane proteins and every one of those integral membrane proteins represents a structure called an acetylcholine receptor and I'm going to abbreviate the word receptor with an R and a circle around it okay now suffice to say this is our sarcolemma our cell membrane now deep inside the cell I'm going to have one of these myofibrils and my final 5real it's gonna have my z line like this with my actin filaments sticking in both direction I'll have another z line here with some more actin filaments and this holding will repeat this is my mynah fiber oh and you get the picture I'll have my myosin filaments my myosin filaments we've studied the structure of a sarcomere you should know it very very well and so on and so forth and one of the things I'm going to do at this point is I'm going to draw the sarcoplasmic reticulum on our models that happens to be yellow in lab and here's a section of sarcoplasmic reticulum here's the terminal cisternae here's the sarcoplasmic reticulum extending the length of the sarcomere near the zones of overlap is where the terminal cisternae are and I have all these cisterna coming across and one of the things we learned previously is that the sarcoplasmic reticulum is a calcium reservoir and stores a lot of calcium ions now there's an opening or invagination at the cell membrane that will run all the way through the cell that we call the t tubular a transverse tubules and there would be another one over here running on this side and another turtle sarcoplasmic reticulum I'm going to leave this one exposed as if we've peeled all the sarcoplasmic reticulum off so now we're almost set up for us to understand how the muscle contracts so I'm going to use red to represent my voltage here but there's going to be a voltage and current that travels down the axon how and why you're going to learn when we do neurons that's a whole nother lecture as complex as this one so suffice it to say that there's a voltage called an action potential and I'll abbreviate it as ap from here on it and that voltage is going to be traveling down the neuron down each to load entry on in the membrane and it's going to hit the synaptic knobs one of the things we know about synaptic knobs is they have membrane proteins called calcium ion channels earlier in the semester we talked about sodium channels we talked about potassium channels and we talked about how ions can flow into or out of the cell and we talked about the sodium potassium ion exchange pump well in skeletal muscle cells and in neurons we have voltage-gated channels channels that are closed but can open with a certain voltage when we shock them they open when we stop shocking them they close they're called voltage-gated channels this particular channel which lives there's tons of them in each synaptic knob are called calcium ion channels or calcium voltage-gated channels so there's tons of calcium ions outside the neuron floating in the extracellular fluid there's a much higher concentration of calcium ions outside the cell then there are inside the cell and so if I were to open these channels due to the laws of diffusion calcium would come rushing into the synaptic nam there are proteins in the membranes of the vesicle that can also bind to the proteins in the cell membrane and cause them the fuse and release the neurotransmitter by exocytosis all i need to do is open those voltage-gated calcium channels calcium would rush in the synaptic vesicles fuse with the synaptic not membrane and release the neurotransmitter into this gap this space happens to be called the synaptic cleft now my picture is getting rather messy but we still need to talk about that gap so I'll label it or actually you can label the neuron drawing with this gap is called the synaptic cleft a cleft is a gap now once the neurotransmitter is released into the synaptic cleft it's going to diffuse out it's got no choice but to bump into the acetylcholine receptors and what I didn't draw for you a moment ago is this the acetylcholine receptors are attached to another ion channel called a sodium ion channel and so there's another protein here that's a sodium ion channel and again there's even more sodium outside the cell as well each acetylcholine receptor is attached to a sodium ion channel when I bind acetylcholine to the acetylcholine receptor the ion channel will open and sodium will diffuse into the skeletal muscle cell so quick rundown when the action potential travels down the axon it spreads down the T load end RIA and reaches the synaptic knobs at the synaptic knobs it's going to shock these calcium channels into opening as soon as the voltage hits them and when the voltage the actual potential reaches these voltage-gated calcium channels calcium ions will diffuse into the cell but that's when of course is that the synaptic vesicles begin fusing their synaptic membranes or their vesicular membranes with the cell membrane this is simply the process of exocytosis and a certain quanta or amount of neurotransmitter will be released into the synaptic cleft as the neurotransmitter acetylcholine is released into the synaptic cleft it begins binding to acetylcholine receptors once it binds to these acetylcholine receptors the sodium channels open and these are called chemically gated sodium channels I think I said a minute ago please forgive me these are chemically gated sodium channels and the ion sodium will start to diffuse in and bring some positive charge into the cell changing the voltage of the membrane and because these voltage comes are these chemically gated sodium channels are allowing voltage in very close to these chemically gated sodium channels are going to be voltage gated sodium channels and when the voltage hits these voltage gated sodium channels the right amount then they open and even more sodium will pour into the cell and that will cause the next voltage gated sodium channel and then the next one to open and we can see how the voltage will diffuse into the cell and diffuse from areas of high concentration to lower concentration hitting the next channel and the next channel and so on and so forth and these channels run all the way down the teaching tools so once I start the action potential in the skeletal muscle cell membrane in the sarcolemma that action potential is going to travel all the way through the sarcolemma and all the way down the sarcolemma in all directions at around and as it encounters the t-tubule the action potential travels down the t tubules and then it's going to hit the sarcoplasmic reticulum but lipids can conduct action potentials pretty well so if i grabbed onto something and it shocked me with a high voltage and you grabbed in my arms skin-to-skin then it would shock you as well and since this membrane is touching this membrane the terminal cisterna is touching the t tube you'll that's going to cause the action potential to spread throughout the sarcoplasmic reticulum the sarcoplasmic reticulum just like the synaptic knob has a bunch of calcium ion channels so if i drew on a large piece of sarcoplasmic reticulum here sorry i dropped a marker with the terminal cisternae and some of the other sister knee here so when the voltage travels down the g-tube you'll hear and shocks the sarcoplasmic reticulum the sarcoplasmic reticulum has a tip cell membrane or in its membrane it's not a cell membrane and as calcium channels and when the voltage hits these calcium channels and they open all the calcium ions that are stored in the sarcoplasmic reticulum are going to be able to diffuse out into the cytosol of the skeletal muscle cell so essentially this piece of circle plasmic reticulum would be sitting here like this and as the calcium channels open which is where the action potential the calcium ions will diffuse out by the troponin and like we saw on the last video the troponin will change shape and pull tropomyosin off the active site and when that happens here the whole piece will flip over here as long as calcium is bound to the troponin troponin will change its shape full tropomyosin off the active site and that's going to expose the myosin on the active sites on the actin that will allow myosin heads to begin flexing their hinge binding the cross bridges and then it's going to power stroke and while one is bound and pulling the other one might be reaching up and just like a series of arms they'll grab and pull grab and pull grab and pull as long this calcium is being pumped out and the troponin has changed shaped and has the active site exposed the myosin heads will continue to pull that's going to pool the z lines towards the M line causing the muscle to contract I have a numbered series of steps in my notes set and I will run through them verbally with you but essentially in the first step the action returned actual potential travels down the axon down the TiVoed Andrea and shocks the calcium channels in the synaptic knobs in the opening calcium will enter the synaptic knob causing the synaptic vesicles to fuse with the cell membrane and release the neurotransmitter acetylcholine acetylcholine will bomb across the synaptic cleft bind to acetylcholine receptors opening some chemically gated sodium channels in the sarcolemma if enough sodium reaches leaks in causing it to reach threshold then voltage-gated channels will begin opening that will start an action potential through the sarcolemma membrane and that action potential will spread all the way down all the way down the t tubules so as the action potential travels down the t tubules it's going to shock the circle plus particular matter releasing calcium and then calcium is going to bind to troponin troponin is going to change shape and pull tropomyosin off the active sites and the myosin heads can grab and pull and as long as my brain is sending the signal and I continue to release neurotransmitter the muscle will stay contracted and contracted and contracted those are the steps of muscle contraction now there's a lot going on but hopefully you can start to see the anatomy all come together and the physiology there are some really cool videos that are associated with our textbook and some online that show this sort of in a cartoon or computer animated series of steps and you need to watch those now the last thing that we need to do is we need to cause the muscle to relax okay before I do that I want to give you an analogy imagine if I had a rope almost like the velvet ropes you know how they have the little stands at a movie or some places that have the little loop here that the rope hangs through and will go to the next end and so on so imagine if we were standing here like this ready to grab these ropes and a tug-of-war and let's say we're gonna have a tug-of-war with another instructors class and whoever wins this tug-of-war whoever pulls us in flag hanging off here at certain distance in either direction would win this tug-of-war that class would all get ace for the rest of the semester and free tuition next semester I don't know it's not gonna happen but imagine that and all of us are lined up here as soon as I let you grab the rope the rule is as soon as you can see the rope you can get up and start pulling what if I took a piece of PVC piping then white plastic pipe that you make coming out of and slid it through here like this so that you guys couldn't see the rope now the rule is the instance that the Rope is available to you you grab and start pulling you were essentially the myosin molecules the Rope would be the actin molecules well when I start pulling the PVC pipe off the first person that can see it starts grabbing and pulling with their arms arms representing myosin filaments the next person would grab and pull and grab them we don't all want to grab and pull and then let go with both hands because then we would all lose the tension that we provided so we're grabbing and pulling like this and handing the rope back as long as it's exposed now what if when you're reaching out you start to release and I start sliding the pipe back over and before you could grab on with this hand you let go with this hand and I covered the pipe I mean I cover the rope now you can't grab so as long as the tropomyosin is pulled off and exposing the active sites on actin the myosin heads can grab and pull and contract the muscle when we're going to relax we're simply going to reverse all the steps we're simply going to remove the calcium the sarcoplasmic reticulum actually has a calcium pump that works very similarly to the sodium and potassium pump it can pump a couple of calcium ions back in and it requires ATP to do so if I start pumping the calcium in and remove all the calcium from the troponin it will go back to its original shape and block the active sites on actin and then the myosin heads would be able to grab and pull and really what we do is we go back to the beginning for all of this to end my brain stops sending the actual potential when I stop shocking the calcium channels the calcium channels closed if I closed the calcium channels no more calcium can enter then what happens as a calcium pump is actually pumping calcium back out like the sodium potassium pump with no calcium available the remaining vesicles can no longer bind and release neurotransmitter now once the neurotransmitter released ends it turns out that there is an enzyme I didn't talk about yet I was saving it for now there's an enzyme that lives in the synaptic cleft called acetylcholine esterase and that's what these little X's represent they represent a model molecule called acetyl choline esterase it's an ace it's an enzyme that happens to break down acetylcholine it breaks an ester bond in the molecule breaking it into acetate and choline so acetyl choline esterase is the enzyme that breaks down acetylcholine in the synaptic cleft and acetylcholine esterase has the abbreviation ACH II capital a capital CH and II acetylcholine esterase us essentially acetylcholine esterase breaks down all the acetylcholine in the neuron and the synaptic cleft once all the neurotransmitter is released these sodium channels close no more ions can come in the sodium potassium pump will restore everything as all the ion channels closed when the voltage of the cell membrane stops then the voltage down the t tubules will stop which stops sucking the sarcoplasmic reticulum all those calcium channels would close and then we actively pumped all the calcium back into the particular as I remove the calcium here and pump the calcium back in using a calcium pump the troponin will go back to its original shape putting tropomyosin up over the active site the myosin heads can no longer bind so if I remove all of this and I put the tropomyosin back over the active site I know it's getting a little messy here then the calcium with the calcium removed troponin places tropomyosin back over the active site the myosin heads can't grab and pull so they just sit there waiting the next time I said an action potential I shocked its calcium channels into opening and the synaptic knobs calcium enters the synaptic knob and causes the synaptic vesicles to release the neurotransmitter acetylcholine into the cleft acetylcholine binds to the acetylcholine receptors causing an action potential to spread all the way down the sarcolemma down the T tubules and shocks the sarcoplasmic reticulum in releasing calcium calcium binds to troponin troponin changes shape and pulls tropomyosin off the active site the myosin heads grab and pull in the muscle contracts in order for relaxed relaxation to occur the action potential ends the calcium channels closed and we pump the calcium out we stop releasing neurotransmitter the enzyme acetylcholinesterase breaks down all the acetylcholine in the synaptic cleft which ends the action potential in the circle and MNT tubules which causes the sarcoplasmic reticulum to close its calcium channels pump actively pump all the calcium back in removing calcium from troponin troponin changes shape and goes back to its original spot pulling the tropomyosin over the active site and now the myosin heads can grab and pull and they're sitting there waiting I expose them they pull I stop exposing them they sit and wait that's what causes the muscles to contract and relax contract and relax it's a bunch of complex steps this v I've written it out in five steps in my note set for muscle contraction and then six through ten of the steps for relaxation and there will be a worksheet for you guys to fill in some stuff help you review this material so please watch the video a few times do the worksheets fill in your notes set and start preparing for the quiz if you're not in my EMP class I hope you learned something I hope you glean some information from this and I hope it was helpful again this is sort of a basic and fundamental approach it's not all the detail that we can get into but we could go on forever and have to our videos and I'm not going to do that so I hope this was helpful hope you had as much fun as I did I'll see you on the other side