Skeletal Muscle Mechanics Biomed Physio Exam 2

Non-optimal lengths can happen. So if you stretch your muscle out, you have probably noticed that you have less force generation capacity. That is another reason why It is easier to hold a mass close to your body with your arm. As opposed to outstretched. Close to your body's center of gravity, your muscles are all at or near optimal length. But as you stretch it out , they stretch and now they are at non-optimal length. ________________________________________ Were you paying attention? Factors Affecting the Force Generated by Individual Muscle Fibers 1) Nonoptimal lengths *When they are greater than optimum: -(Increase/decrease) crossbridge overlap *When they are less than optimum: -(thick/Thin) filaments overlap each other -Z lines contact (thin/thick) filaments

!) Decrease ;thin; thick

Summation occurs for one simple reason: The differences between these two numbers. An action potential takes roughly 2 msec to complete. Whereas, a muscle fiber remains contracted for anywhere between 10-200 msec. What this means is that we can hit a muscle fiber with multiple action potentials before it has had a chance to fully relax. And that is going to allow those individual twitches to sum. There are two types of summation: complete and incomplete. Incomplete is also known as unfused. And complete is also known as fused. The idea is that incomplete leads to complete. We call it incomplete because there are still small oscillations in the force about the peak. We are not maintaining maximal force at this time. We are getting there. Staying there but only briefly. And the starting to drop back down and then we hit it. And back up and back down. This is because we have not yet released enough calcium to fully expose all of those binding sites. So we do not yet have the full number of cross bridges forming. If we continue to stimulate that muscle fiber with more and more action potentials, then we will build to this. Complete or fused summation. We are maintaining those calcium levels at peak. So we are releasing it from the SR stores faster than it can be resequestered. Any further stimulation beyond this point will not result in any increase in force. That is it. That is as much force as you are going to get out of that little muscle fiber. It has peaked. And so, when that complete or fused tetanus occurs, we refer to that as maximal tetanic contraction. That's it. As high as she goes. All of the cross bridges that can be formed are formed. All of the actin-myosin binding sites that exist, are exposed. ________________________________________ Were you paying attention? Factors Affecting the Force Generated by Individual Muscle Fibers Basis of summation 1) How long does an action potential last? 2) How long can contraction llast? 3) True or False: Contractions can overlap and sum 4) What is tetanus?

1) 2 msec 2) 10-200 msec 3) True 4) Peak of summation

Simple formula. High frequency stimulation release of calcium exceeds reuptake. Eventually the system though is saturated. There are only so many cross bridges that can form physically. Once that number has been reached it makes sense that we will not be able to generate any more force. Everything is saturated. That is when we reach maximal tetanic contraction. ______________________________________ Were you paying attention? Factors Affecting the Force Generated by Individual Muscle Fibers Cause of summation and tetanus 1) Amount of tension developed depends on amount of ______ bound to troponin 2) At high frequencies, release exceeds ________ *Ca2+ increases in _______ 3) Eventually saturates system *All troponin has ______ bound to it *_________ cycling maxed out *Maximum _______ contraction

1) Calcium 2) Reuptake ; cytosol 3) Calcium ; cross bridge; tetanic

The other factor to consider is diameter of the fiber. Straight forward. The larger the diameter, the more force we can generate. Larger diameter fibers have more filaments. Weight lifters have large buldging muscles for a reason. Because when you are lifting weight, your body's response to that is to undergo hypertrophy. We are born with the maximum number of skeletal muscles you will ever have, All you can do throughout life is make them bigger. How do you make them bigger? You pack in more of those contractile elements. More actin, more myosin into the cytoplasm. As that cytoplasm expands, the muscle expands. There are some studies that indicate that we do have a limited regenerative capability in our skeletal muscles. Those satellite cells that hangout in the connective tissue surrounding the skeletal muscles. Those are stem cells that can differentiate into muscle forming cells and under some limited situations Replenish our stock of muscle fibers. But How to get them to do this under physiological conditions, Is a matter of some fate at the moment. What we have to live with for now, is simply enlarging the muscles that we have. And that works fine. We get More fibers, more cross bridges and more force. _______________________________________ Were You Paying Attention? Fiber diameter 1) Force-generating capacity = inherent (built-in) ability of muscle to generate ______ 2) Force-generating capacity depends on the number of ________ in each sarcomere and the geometric arrangement of ________ *More crossbridges/sarcomere --> more ____ *More sarcomeres in parallel --> more ____ 3) Number of thick and thin filaments/area = constant *Fiber diameter (varies/same) *(Larger/smaller) diameter --> more filaments --> more ______

1) Force 2) Crossbridges ; sarcomere ; force ; force 3) Varies ; larger ; force 4)

1) So this is treppe, notice that the action potential frequency is not such that we are interrupting one of these twitches. The twitch is completed. Rises to peak and falls back down to baseline. Rises to peak, falls back down to baseline. So we are not interrupting the twitch in treppe. We are warming up the muscle fibers, stretching them out. Getting those calcium levels a little higher, warming up those series elastic elements. Series elastic elements= Connective tissue that surrounds the muscle fibers. Eventually we will run into the tendon; help form part of the tendon. And so we stretch those out, makes it easier to generate to peak force. Were You Paying Attention? 1) Are you interrupting the twitch in treppe? 2) What are you doing in treppe? 3) What are series elastic elements?

1) NO 2) Warming up muscle fibers ; stretching them out 3) connective tissue that surrounds the muscle fiber 4)

How is this possible? The larger that axonal diameter, the more it takes to depolarize that fiber to threshold. If you think about it, we are talking about ions moving across the membrane of that axon fiber. SO it makes sense that if our fibers are very large, It is going to take movement of more ions to depolarize it. Whereas a very small axon fiber doesn't need movement of as many ions to generate the same potential. So there we go, that is how we can recruit motor units based on size. Large motor units are innervated by large diameter axonal fibers. Small motor units are innervated by small diameter axonal fibers. As your body encounters the force, it starts small. That is why we don't smack ourselves in the forehead when we pick up a phone. Your body will evaluate the amount of force it is being asked to generate, if those small motor units can get the job done, then kudos. If not, action potential frequency will increase. more firing of actional potentials will lead to greater depolarization, will lead to depolarization of large diameter fibers. And we recruit those large motor units to generate a lot of force. And your body is no fool. It is designed very elegantly. Such that motor unit size and fiber diameter are correlated. Small motor units tend to have mostly very small fibers. That makes sense because we are going to be using those for fine and delicate movements, so we don't need a lot of force. Large motor units have very large muscle fibers. So we can bring as much force to bear as we can. ________________________________________ Were you paying attention? Regulation of the Force Generated by Whole Muscles 1) The Size Principle *Order of motor unit recruitment is related to ____ of motor units *(large/small) units recruited first *(small/large) units recruited last -(smaller/larger) neurons are more difficult to depolarize to threshold -Requires greater synaptic input -(large/small) neurons excited first (low input), then (small/large) neurons (high input)

1) Size ; small ; large ; larger; small ; large

How does your body recruit these motor units of different sizes.? The answer is in the way that they are innervated. So when we fire that motor unit, all of the fibers within that unit have to contract. So To increase force, we need to recruit more motor units. The first motor units to be recruited are always going to be small. We have motor units that only contain 3 muscle fibers. Very delicate movements. Think about your extra ocular muscles. The 6 muscles that surround the eye and control its movement. Very small movements, very fine control. Muscles for strength tend to have more large motor units. Muscles like your biceps would have a larger proportion of very large motor units. Generate a lot of force. We recruit those motor units based off the size principle. The order of recruitment is based off size. Small motor units are recruited first. Large motor units are recruited last. SO for fine control and fine manipulation of objects, All we need are those fine motor units. ________________________________________ Were You Paying Attention? Regulation of the Force Generated by Whole Muscles 1) Motor unit recruitment * More fibers contracting --> Greater _____ *Recruit motor units -Activation of the motor neuron activates all muscle fibers in the ____ ____ -Increases in tension occur in steps proportional to the ______ of the motor unit *Muscles for delicate movements -(small/large) motor units *Muscles for strength -(small/large) motor units

1) Tension ; motor unit ; size ; small ; large

1) How we build to peak force with our muscle fiber has to do with this: the frequency with which that muscle fiber is stimulated to contract. So those isometric contractions, those are only reproducible all or nothing events if the muscle is stimulated at a frequency low enough to ensure separation between the individual twitches. We have been looking at is that: single isolated twitch which is the foundation of all muscle contraction. Turns out that this alone will not get us to peak force. We need to build upon this. There are a couple ways that this occurs. One is called treppe. And the second way is summation. Two closely related but different things that we need to talk about. Treppe occurs when we are stimulating that muscle fiber at a high enough frequency that the independent twitches follow closely one after the other. And so peak tension in treppe is going to rise in a step wise manner. This term treppe means stepwise. So tension will rise in step wise manner. We are not entirely sure why treppe works. But the best guess is that treppe stretches the muscle fiber. So it is sort of like a warm up exercise for individual muscle fibers. The more it is stretched, the warmer it gets and the easier it is for it to spool up to peak force. If you have ever picked up a strong elastic band like the one you use for working out -very high pull that you need to stretch it. What you will notice is that taken out of the box cold that stretch is very hard, it takes a lot more force. If you keep stretching and relaxing it, It gets easier with each subsequent pull. This is what we are talking about with treppe. The other theory is related to cytosolic calcium levels. This theory holds that what happens in treppe is that because the frequency of action potential firing is so rapid, that we don't really allow calcium levels to fall back down to baseline. In other words, some cytosolic calcium is left and hasn't been sequestered back into the sarcoplasmic reticulum. So obviously that would speed things up a bit because now we don't have to wait as long for those events of excitation-contraction coupling. That lag is going to be reduced. There is evidence to support both theories. It is probably the case that both of them play a role in treppe. Treppe will cause us to reach peak tension, but only ever so briefly. Each of those twitches will be right up at max. But you wont be able to make use of that until we start summing - summation. Action potentials arrive before each individual twitch can be fully completed. In other words, what we have here is a case where the action potential is firing here and that stimulates it to rise up here, maybe we have another action potential here, and another one here. So before that twitch has a chance to fully complete (rise to peak and then back down to baseline). We hit it with another action potential. What happens then is that the twitches become super imposed on one another and they add. And that will yield a force greater than any individual twitch could reach alone. So we are not interrupting the twitch in treppe. We are warming up the muscle fibers, stretching them out. Were You Paying Attention? Factors Affecting the Force Generated by Individual Muscle Fibers 1) Frequency of stimulation: increases in the frequency of action potentials in muscle fibers increase tension in two ways * _______ * _______

1) Treppe ; Summation

This is why we can get to that point. Action potential time scale. Muscle contraction time scale. Vastly different. 1) True or False: Multiple action potentials can stimulate a muscle before it has had a chance to relax. That is the basis of summation. That is how we get to this point: maximal tetanic contraction.

1) True

Factors that influence the amount of force that muscles generate. For an individual skeletal muscle fiber, an action potential is an all or nothing event. What we mean by that is that that muscle fiber that is innervated by that particular motor neuron is going to contract not necessarily fully, but it is going to start the process of generating maximal force. There are a couple of things that affect this force that it can produce. One is size, the larger that muscle fiber and cross-sectional area, then the more cross bridges there are. The more cross bridges = the more force. Another way is by recruiting more muscle fibers to contract. All the skeletal muscles in our body are made up of bundles of muscle cells. So when that muscle contracts, not all of those muscle cells are going to be stimulated to contract. This is a good thing, bc it allows us to manipulate objects in our environment delicately. We can reach down and pick them up with just the right amount of force. Were you paying attention? Factors Affecting the Force Generated by Individual Muscle Fibers 1) Graded muscle contractions depend on how many factors? 2) ______ produced by each fiber *Number of active ____ ____ that bind to actin *More crossbridges that bind --> more _____ 3) Number of fibers ______

1) Two factors 2) Tension ; cross bridges ; force 3) Contracting

We have been talking about single muscle fibers, but our muscles are composed of bundles of fibers. Think about this. The difference in force generation between a single isolated twitch and maximum tetanic contraction. Guess how much that is? 5 times. From a single isolated twitch all the way up to peak force generation. That is not much. That alone does not explain the range of forces that we can bring to bare. So The other factor to consider is that these muscle fibers were not operating in isolation. And your body can take advantage of a phenomenon called recruitment. Recruitment means drawing in more muscle fibers to contract. Calling on them to bring their force to bear on whatever task is at hand. Recruitment is the final piece of the puzzle that can explain the wide range of forces that we are able to generate . So a muscle like your bicep is nothing more than a bundle of muscle fibers. More muscle fibers contracting equals more tension. Recruitment occurs at this level. The Motor unit. Motor unit is comprised of a motor neuron and all the fibers it innervates. Motor units vary in size. Some are large, some are small. Within a muscle like your bicep muscle, there are variously sized motor units. When you contract your bicep, if I were to pick up this marker. Not every muscle fiber in that bicep muscle is contracting. It doesn't need to, it is just picking up a marker. Some of them are just going along for the ride. If I were to try and pick up something heavier, then more muscle fibers would be brought to bare. Then we can call on the reserved muscle fibers, the ones that had just gone along for the ride before. It is now going to be kicked into gear. That is how recruitment works. The more force we need, the more muscle fibers we stimulate. And so we can call upon more motor units. ------------------------------- Were you paying attention? Regulation of the Force Generated by Whole Muscles 1) More muscle fibers contracting --> greater ______ 2) Recruitment *Stimulating more muscle fibers to ______ *Muscle = bundle of _____ ____ *More muscle fibers contracting --> greater overall muscle _______ *Recruitment occurs at the level of the motor ________

1) force 2) contract ; fibers ; tension ; unit

Now, when we are contracting, isotonic, more load on the muscle, equals more what? It takes more time to generate force. Excitation-contraction coupling. So that lag period increases as load increases. You know this. You can pick up the marker off the desk a lot faster than you can pick up the whole desk. So that velocity of shortening is going to change depending on the load you are placing on that muscle. SO more load means it takes longer to generate more force. ------------------------------- Were you paying attention? Velocity of Shortening 1)When muscle contracts isotonically *Latent period of shortening (increases/decrease) with increasing load *Duration of shortening (increases/decreases) with increasing load *Velocity of shortening (increases/decreases) with increasing load -Rate of change of the distance is shortened -Reaches 0 when load (greater than or equal to) maximum tension -Greatest when no load on muscle

1) increase ; decreases; decreases

Another factor that can play a role, although less of a role for us, is the length of that fiber when it was stimulated to contract. So every muscle in your body has a so-called optimal length. This is the length at which it can generate maximal force. The reason being this. At that length, there is maximal overlap of those thick and thin filaments. Remember this? Our sliding filament model, we want them to slide past each other. This makes sense. If your muscle is too long, there is not going to be much overlap between those thick and thin filaments. When muscles are too short this happens. Now instead of pushing and sliding past each other, they come into contact with the myosin. If you Remember the Z line, and then you have your little myosin heads here. Here are you thin filaments. So now when these things get too close together, these myosin ends sort of block this sliding of the sarcomere. Remember sarcomere runs Z disk to Z disk. Those myosin fibers prevent the Z lines from sliding towards each other any further. You are not able then to generate anymore force because the sarcomere is working against itself. Conveniently inside the body, most skeletal muscles are at optimal length. What keeps them there? Skeleton. They are anchored, in most cases, to bone. Those bones fix the ends of the muscles. And ensure at rest under physiological conditions those muscle fibers are at or near their optimal length. ________________________________________ Were you paying attention? Factors Affecting the Force Generated by Individual Muscle Fibers 1) Fiber _______ *Length of fiber at the onset of ________ affects force generated 2) Optimal _______ *______ length of muscle at which the fiber can develop the greatest amount of tension *Due to maximum _______ of thick filament crossbridges and thin filaments * In situ, most muscles are at optimal _______

1) length ;Contraction 2) length ; resting ; overlap ; length

When you exercise, you tear muscle fibers. You a limited ability to regenerate the connective tissue surround them because there are all sort of stem cells hanging out in that connective tissue that can do just that. It will be slow depending on how vascularized it is. SO the larger the tear, the slower it will be. There is some evidence to suggest that if you lose a muscle cell, you can stimulate those satellite cells to divide to replace it. But generally what happens and this is especially true when you are weightlifting you are causing microscopic tears in those contractile elements of the muscle fiber itself and those will be replaced by additional contractile elements so that does not happen again. When you exercise very heavily, when you are weightlifting, One of the tale tell signs of this can be the process of a lot of protein in your urine. And One of those proteins could be myoglobin. Myoglobin is the tissue storage form of hemoglobin. Hemoglobin binds to oxygen in your blood. Myoglobin binds to oxygen in certain muscle fibers. When you exercise, you tear those saromental membranes you allow contents from the sarcoplasma to leak out. And they will eventually find their way to the blood. And into your urine. So you are causing millions of microscopic tears in your muscle fibers when you lift something heavy. ________________________________________ Regulation of the Force Generated by Whole Muscles 1) Motor unit sizes *Size of the motor unit and fiber diameter are often related -Small motor units --> (small/large) fibers ~Small motor neuron cell bodies ~Small axon diameters -Large motor units --> (small/large) fibers ~Large motor neuron cell bodies ~Large axon diameters

1) small ; large;

Different muscles in the body are optimized for different tasks. We find that they have different proportions of large and small motor units. This is basically rehashing of what we have been talking about. ------------------------------- Were you paying attention? Regulation of the force generated by whole muscles 1) Motor unit sizes *Number of motor units (varies/same) in different muscles *Size of motor units varies -(Large/Small): for delicate movements -(Small/Large): for strength movements *Fiber diameter (and thus strength) (varies/same) in motor unit -(Small/Large): for weaker movements -(Small/Large): for stronger movements

1) varies ; small ; large ; varies ; small ; large