okay class welcome back and today in this lecture we're going to start talking about skeletal muscle and we're going to discuss the structure of skeletal muscle and we're going to talk about skeletal muscle function in particular muscle contraction okay so we have four main classes of muscle cells so we have these skeletal muscle fibers which we're going to talk about today we have heart muscle cells or cardiac muscle which we will talk about later we have smooth muscle cells we will also discuss these not in this lecture but in this module and we also have myoepithelial cells as you see here that are present in some exocrine glands here's a question pause and see if you remember this from your undergrad physiology studies so skeletal muscle anatomy um we start off by looking at the we have a large muscle right like the biceps um in this scenario and the muscle is made up of a muscle fasciculus which is made up of a group of muscle fibers and every muscle fiber is actually made up of a bunch of myofibrils if we take a deeper look the myofibrils are made up of the functional unit right or the sarcomere and the sarcomere is composed of different myofilaments if we zoom in here you will see that we have the z disc right here and so between every z disc and another that's basically what a sarcomere is and then you can see that we have the thin filaments right over here and these are your actin filaments and we also have the thick filaments that you see here and these are your myosin filaments you can see this spring-like structure right this is titan a very important protein and if we take cross-sections at different parts of the sarcomere like here for example this is what it's going to look like if we take a cross-section here you're only going to see the myosin fibers if you take a cross-section here it's going to look a little bit different and if you take one here where you're actually you're going to see both the myosin and the actin filaments in cross section and you can see how the myosin filaments are arranged right with the cross bridges facing outwards right these are the little bumps that you would see here and here's an individual myosin molecule right composed of the light mirror myosin and the heavy neuromyosin which has the crossbridge activity looking at the actin filaments f actin so f is for filament but the actin filament is actually made up of a bunch of different [Music] actin molecules right or g-actin molecules that come together and polymerize to make up the actin filament so this basic structure of the sarcomere it's a genius structure it's incredibly efficient and it just it's a great piece of art because once you realize how this sarcomere works um it's it's just incredible so again muscle fasciculus fiber myofibril and then myofilaments and sarcomeres so taking a look at the muscle fiber which is made up of a group of different myofibrils um the muscle so these myofibrils they come together and they make an individual muscle fiber it's a multi-nucleated fiber so you can see here multiple different nuclei are present when you're looking at the sarcomere under a light microscope you will see the light bands in the dark band so the light band is where you only have actin so it's going to be this part right here you only have actin while the dark band you will have actin and you will also have myosin and they will be overlapping right so again z disk and z disk right this is what makes a sarcomere so this is going to be an individual sarcomere all of this right here you're going to have a period of or a region that's going to be the light band where there's only actin on both sides and then you're going to have the dark band in between and so when you have a muscle contraction basically what's going to happen is that the z disc this c disc is going to move in this direction that z disc is going to also move in that direction and they're going to come closer essentially making the sarcomere shorter in length in the contracted state compared to the relaxed state that you see right here actin so actin is not just found in muscle cells actually actin is a very important component of the cell cytoskeleton you can see that right here so actin here is in red and you can see how it's just forming that cytoskeleton and giving cells their shape so actin helps in determining the shape of the cell surface actin is also pretty important in whole cell locomotion we're going to talk about that and the actin filament you can see it here under electron microscopy it's made up of these globular units right the g actin subunits and these g actin subunits are going to come together they're going to polymerize and then they're going to make up the actin filament we mentioned actin's role in in cell locomotion right and so you have these small soluble units they are going to polymerize into these filaments and if you have a signal right such as a nutrient source in this case these filaments are going to disassemble where you're going to get the basic subunits and then they're going to start to reassemble again in the direction of that stimulus causing the cell to move in an immediate motion towards the site of the stimulus so pretty cool so again the message here is that actin plays a larger role than simply a scaffolding for the sarcomere for the myosin cross bridges to hold on to so it has many different roles in different cells and it's an essential component of the cellular cytoskeleton actin is also associated with multiple um accessory proteins um so here's an example in the contractile bundle where we have alpha actinin alpha actinin is an accessory protein that helps um scaffold and hold the actin filaments apart so they they're not super close to each other so if you're thinking of a muscle cell in a sarcomere you need some space for those cross bridges to come in and bind and so alpha actinin provides that spacing if in in some genetic disorders you may not have alpha acted in and that's going to be a big problem for the sarcomere because you will not be able to have sufficient contractions finbrin is another form of accessory protein and if you have fibrin instead of alpha actinin you can see here the tight packing prevents myosin 2 from entering and if myosin 2 can't enter then it can't latch onto the actin filament and therefore contraction will not be possible here you can see alpha actin and under electron microscopy and how it looks like so um there are a lot of different types of accessory proteins this slide just shows you um how many they can be so tropomyosin is another one right that we're familiar with and triple myosins help stabilize the actin filament because remember the filament is made up of these subunits and so the subunits can polymerize but what prevents them from depolymerizing in skeletal muscle what prevents them from doing that is tropomyosin tropomyosin helps stabilize that filament capping proteins right they would come and they would cap the actin filament so it maintains its length we already talked about alpha actinin so again the idea is that a lot of different accessory proteins are very very important and a lot of muscle dystrophies have to do with genetic disorders in some of these proteins now myosin ii a member of a larger super family of myosin proteins and myosin proteins are a member of motor proteins meaning these are proteins that actually have movement properties skeletal muscle myosin was the first motor protein identified and it was called myosin ii because it has two heads so this is the one that we are going to be talking about um you can look at the myosin two structure where you have the uh the two heavy chains right that you see here and then you have the two light chains as well and this is what it looks like under atomic microscopy very very very cool now these individual myosin proteins that you see here they're going to come together and they're going to be arranged in this to form this thick filament or the myosin ii filament you see here an individual myosin protein here's the myosin tail here are the myosin heads and they just come together forming this myosin filament you see that there's the bare zone right here in which you do not have any myosin heads and so essentially you will have actin filaments here and here here's going to be a z disc here's another z disc actin filament and actin filament and then the myosin heads are going to be attaching to these actin filaments and pulling the two z discs together this way in order to induce muscle contraction the protruding heads these myosin heads that are protruding from the myosin filament are what we're going to call the cross bridges so you're going to probably hear that term a lot um and you're going to hear it often so now you know what it is the myosin filaments are arranged in this uh incredible formation so this is a cross section from an insect flight muscle and i i look at this picture in awe because i i just think that it is incredibly wonderful so you see here the myosin thick filaments right in cross-section and you see that they're surrounded by the actin or the thin filaments that they latch to or they hold on to and it's because of this structure that we actually have muscle movement um here's a pretty cool video uh it's gonna be available on your course page make sure that you um you watch it accessory protein so again we have the z disc that we talked about okay very important here are your actin filaments right we know that we have tropomyosin wrapping around it but on this end you have triple modulin to cap it and we have cap z which is another accessory protein capping the actin filament from the other side we also have titan as you see here the myosin or the thick filament you can see the bare zone and the cross bridges [Music] muscle contraction helps or occurs i'm sorry by sliding of the myosin filament past the actin filament what i want you to keep in mind is that um the sliding happens without any change in the length of either filament so the length of the actin filament doesn't change and the length of the myosin filament doesn't change either it is just that the z discs are being pulled together or towards each other each myosin head is going to cycle about five times per second in the course of a contraction so when when talking and discussing um some of these accessory proteins we talked about cap z we talked about alpha actinin as well nebulin is a pretty important accessory protein right that wraps around the actin filament as you see here in green and nebulan plays the role of a molecular ruler right to help determine what's the exact length of the actin filament that we want the actin filament is going to have a minus end and a plus end the accessory protein that caps the minus end is your triple modulin and the protein that caps the plus end is cap z we also have titan which is a pretty important protein and what titan does is that it works like a molecular spring so if the muscle fiber becomes over stretched titan actually helps pulling pull to helps to pull it back uh in place and titan is a role of a lot of research um and looking at cardiac muscle for example which also has titan there's a lot of uh physiological changes that happen in the tight end protein like a lot of phosphorylations and dephosphorylations that help determine the stiffness of this molecular ruler of titan um and thinking of a disease like heart failure with preserved ejection fraction in which the problem really is inability of the heart muscle to relax in order to expand and accept more blood titan has been found to be much stiffer in in these cases than it normally should be so it's it's a there's a lot of research going on in titan um i just want to point you to the fact that the accessory proteins are very very important for the sarcomeres to work appropriately and efficiently finally um i want to discuss the walk along theory of muscle contraction and and how it works and so we're going to start off in this scenario here where we have an actin filament and you have a myosin head the myosin head is already attached to the actin filament once atp binds to the myosin head this allows the head to be released from the actin filament so the binding of atp helps release the myosin head from the atp filament then atp is going to be hydrolyzed right you will have adp and energy is going to be released the release of energy helps the myosin head back into its starting position okay so the hydrolysis of atp helps the myosin head back into its original position now what is then going to happen is as the phosphate group is released as you see here right this allows for a weak binding a weak binding of the myosin head to a new site on the actin filament what's then going to happen is you can have a wheat the weak binding of the myosin head to a new site on the actin filament this is going to cause release of the inorganic phosphate produced from atp hydrolysis this release is going to trigger the power stroke or the force generation from the myosin head allowing also the adp to um to also be released and the cycle will then continue here's a question for you so make sure you pause your video and take a moment and control of skeletal muscle contraction by troponins so we know we have the actin filaments we have the tropomyosin helping to stabilize the actin filament but we also have the troponin complex and we have troponin eye troponin c and troponin t so troponin i eye inhibits binding of the myosin head troponin t is what binds troponin to tropomyosin and troponin c binds to calcium in order to in order for myosin to attach to the actin filament the ac the myosin binding sites need to be exposed and these myosin binding sites are normally blocked by tropomyosin but once we have calcium available right an increase in the intracellular calcium concentration once that happens calcium binds to troponin c causing a conformational change that pushes tropomyosin out of the way and exposes the myosin binding sites on actin allowing for the cross bridges to come in and attach we have another video on your course page for motion of the myosin heads and a more detailed explanation of crossbridge cycling or the walk along theory and with that we end this lecture thank you so much for listening