CHapter 11- Skeletal Muscle

What are the steps excitation (nmj) in Excitation-contraction coupling(contraction) What is the start of excitation?

1) Muscle AP travels down to T tubules The start of excitation is Muscle AP 2) Causes voltage gated Ca channels to open( in blue) which unplugs the Ca muscle (in green) The voltage gated unit, it is associated with the release channel (this green thing on the SR), it unglugs the pore in the SR (the release channel in green) When the AP comes down they physically move apart opening up the Ca release channel 3) The increase of Ca (in icf) causes Ca to bind to troponin which causes a a confirmational change of tropomyosin exposing the myosin binding sites on action Yanks the tropomyosin away from its blocking site so a crossbridge cycle can begin and it only begins when the muscles are contracting

What is the process of the Contraction Cycle? (LOOK AT PPT and notes in google docs)

1) Myosin head is in high energy state-cocked position This myosin has ADP plus the inorganic phosphate so this energy that is released is used to cock the head and that head is now storing that energy. 2) Crossbridge Formation Myosin binding sites on actin are exposed, the myosin head will bind to the actin 3) Power Stroke: myosin grabs onto the actin and pulls inward so now its using that energy for movement or sliding the filament (the arrow shows that), so the filament sliding past; during this process ADP falls off and for myosin head to detach requires a new ATP 4) Detachment requires a new ATP ADP is released and now we're adding ATP which allows detachment of myosin head. The energy is in the ATP, the myosin head is in a low energy state, ATP is split to ADP and the myosin head recocks and now its in a high energy state ready to do another crossbridge cycle.

How do you stop the signal in ECC? How does it go back to its resting state?

1) No more AP along the motor neuron 2) Removal of Ach by Ach-ase remove n't' (Ach) by Ach-ase, and we have to get rid of Ca ( remove Ca by putting it back where it came which is the SR; we get it back in by a pump; we put ATPase since its active and were pumping Ca back in); when Ca is removed troponin moves back to original position yanking tropomyosin into its blocking position in which the muscle then relaxes.

Questions to Consider:

1. What is occurring during the latent period? 2. Notice that the relaxation phase is longer than the contraction phase. Consider the role of calcium and come up with a reasonable explanation.

What is a large motor unit? Where in the body would it be found?

A large motor unit might have 2000-3000 muscle fibers and One motor neuron You would have large motor units in your quadriceps, back (postural muscles)

Where does ATP come from?

ATP comes from fuels

What is the contraction period?

After pulling the tropomyosin, myosin heads binds; this period is the crossbridge cycling; during the contraction period we have crossbridge cycling. During the contraction period Ca2+ binds to troponin, myosin-binding sites on actin are exposed, and myosin crossbridges form. As a result, peak tension develops in the muscle fiber.

What is another way to make ATP besides anaerobic and areobic metabolism

Another way to make ATP: in muscle cells there's a storage of creatine phosphate, so this kreatin has a phosphate group on it and that phosphate group is donated to ADP to make a new ATP (so its a one to one).

What happens when your have increase motor units? What is the order?

As you increase motor units recruited you're going to increase muscle tension/strength of muscle contraction. The order of motor units are small to large, small are first (holding something delicate, if you need more strength you recruit larger motor units).

Excitation-Contraction Coupling Where does the AP spread along?

Bc that AP is spreading along the sarcolemma and when it does so it spread sown the transverse tubules bc the transverse tubules are made up of sarcolemma.

Describe the muscle when curling with your bicep muscle

Bicep muscle: We can't change the length of out muscles very much, we're only at this range (on graph) with the max tension: With bicep curls people don't go all the way down bc their muscles are stretched (less crossbridges), so they stay up here. This midrange where there's little change in sarcomere length is where you get most crossbridges (the greatest amount of tension). When the muscle is shorted too much/lengthened more you can only do this so much (curling), its a weaker contraction so thats why people stay up here.

What do hypertrohpy and atrophy do?

Changes in the diameter of a muscle fiber -troph means growth

What do structural proteins do?

Contribute to the alignment, stability, extensibility, and elasticity Holds everything in place It is Dystrophin

What is included when looking at a Length-tension relationship of a muscle fiber?

Down here we have Resting sarcomere length (% of optium) and over here ( tension developed.

What is the relaxation period?

During the relaxation period: the myosin heads deattaches (can't attach again), Ca gets pumped back in the SR. Relaxation period takes longer bc that Ca pump has to pump all the Ca; longer than the contraction phase. During the relaxation period Ca2+ is actively transported back into the sarcoplasmic reticulum, myosin-binding sites are covered by tropomyosin, myosin heads detach from actin, and tension in the muscle fiber decreases.

What happens during the latent period?

During this time, the events of excitation-contraction coupling occur (going back when the NMJ produces an EPP, it then travels producing a new AP. travels down to the tubules, gets the Ca from the SR, Ca binds to troponin which pulls the tropomyosin,) (The muscle action potential sweeps along the sarcolemma and into the T tubules, causing the release of calcium ions from the sarcoplasmic reticulum.) the events occurring here is not nothing, the latent period is a latent period in the muscle but theres plenty of things happening

What is preferred source and the least preferred for ATP production?

Fatty acids are the preferred source and amino acids are the least preferred source. Amino acids environmentally and physiology are expensive sources of energy, they are costly on our livers when burning amino acids.

What does frequency summation allow?

Frequency of Stimulation allows twitch summation

What is glucose? What happens during the day vs when exercising?

Glucose comes from our diet so when you eat, glucose is in our blood. Typically during the day we're burning mainly fats (fatty acids), as you increase the physical activity more and more glucose is burned.

Where is glucose stored? What is glycogen?

Glucose is stored in our liver and in the muscle as glycogen. Glucose is 1 molecule Glycogen is glucose stored in another form. glycogen is all the glucoses stored in the big polymer. Glycogen is the storage form of glucose and its stored in the liver and skeletal muscles.

What are regulatory proteins?

Help switch the contraction process on and off There are 2: Tropomyosin (the long strand that covers the binding site) and Troponin (regulates the position of tropomyosisn) They cover the binding site, myosin heads cant bind if the binding site is covered.

When looking at the length-tension relationship of a muscle fiber, what happens if the muscle is overstretched/sarcomere is streched?

If the muscle is overstretched/sarcomere is stretched these myosin crossbridges can't reach so no tension is developed;

When looking at the length-tension relationship of a muscle fiber, what happens if the muscle is shortened?

If the muscle is shortened too mucb=h, cross bridges can form but the thick filaments will bump into the Z disks and they cant shorten anymore which develops more tension.

What is aerobic metabolism? What are the 2 processes?

If there's sufficient O2 (aerobic metabolism) pyruvic acid enters the mitochondria and in the mitochondria there are 2 processes which is Kreb Cycle and the Electron transport chain. 1)So O2 enters along with 2 pyruvic acids and what is made is a up to 38 ATP and then it produces CO2 and H2O 1 glusocse --> 38 ATP In general, O2 goes into the muscle cell Co2 comes out. iN addition, the mitochondria can also use fatty acids to produce ATP with the byproduct being Co2.

Describe and draw the frequency of action potentials

If you look at the number of AP's coming down it's not a single one, there's a frequency of AP's. There is a frequency of AP's when contracting your muscles and in motor units. And this is in the single muscle fiber (the pics) Graph pic on the left (a): Here we have 1 AP and a single twitch. Pic (b): Here we have some summation, so as the muscle is relaxing a 2nd AP comes up. Pic (c) : Here the 2nd AP arrives sooner, so the muscle just starts relaxing when it gets stimulated again and again and again d): over here the muscle contracts and before it can even enter the relaxation phase another AP arises and so we have a fused contraction called tetanus.

What is a muscle twitch defined as?

Is defined as muscle contraction in response to a single AP (A single AP produces a single muscle twitch)

What is a sarcomere? What is it defined as?

It's a functional unit of muscle and that's the smallest unit within an organ that can perform its function( which is to move your skeleton through contractions) Its defined as Z disk to Z disk, the z disks anchor the thin filaments (made up of actin), the thick filaments (made up of myosin) are anchored by the M line.

What is a motor unit?

Its a a single motor neuron and all the muscle fibers it innervates. Each motor neuron innervates a single muscle fiber. So 1 motor neuron can innervate anywhere from 10 to thousand muscle fibers and that is the motor unit. Every muscle fiber is only innervated once, its only part of 1 motor unit. Here we have the green motor unit innvetated green fibers and the purples too. We have 2 motor units.

What is the structural makeup of myosin?

Its like a golf club with 2 head ( which has functional sites - ATPase and Actin binding sites) ATPase splits ATP and releases energy The arrangement is they are arranged is that the tails are laid inwards with the heads pointing out on opp directions. Myosin, with half of the molecules with their heads in one direction and the other half in the opposite direction

ATP production in skeletal muscle overview (Steps) What is the process called? What is anaerobic metabolism?

So we have blood glucose and muscle glycogen (another storage form) 1)Glucose is split into 2 pyruvic acids by the process called glycolysis and produces 2 ATP 1 glucose --> 2 ATP 2) With pyruvic acid if there is insufficient O2 it is converted to Lactic acid which enters the bloodstream. This process is anaerobic metabolism, (without O2).

How does gradation works? Whats an example of motor unit recruitment?

Motor Unit Recruitment is how gradation works. If you pick up your pencil you only have a few motor units now if you put a book on top you are going to have to recruit additional motor units, and you then put an additional books on top of that then you going to have to recruit more motor units. as you recruit more motor units you increase muscle strength.

What is the NMJ? What is included/produced?

Synapse between a somatic motor neuron and a skeletal muscle fiber Motor end plate ( Muscle membrane) and End plate potential (EPP) (Action potential generated at the muscle membrane)

What is muscle tone? Is it submaximal or maximal contraction? Voluntary or involuntary?

Muscle tone is constant contraction of some motor units, so your muscles have tone (partially contracted all the time). FOr muscle tone it's not a special set of motor units contracting bc you'd be fatigued, it would be a submaximal contraction (not maximal). Muscle tone is involuntary since its always there. ◼ Helps maintain blood pressure - Smooth muscles also has muscle tone, so muscles of the arteries are always partially contracted (they have tone in which they help maintain BP) ◼ Helps maintain posture - helps skeletal muscle

Which is thin filament and which is the thick filament?

Myosin - thick Actin - thing

Describe the trasmisson at the NMJ

So we have our motor neuron causing Ca channels to open release of Ach binding to the cholinergic receptors which produce the end plate potential (which is a large depolarizing graded potential and it is always excitatory), then its going to spread out to the adjacent regions of the muscle cell. So a single end plate potential is large enough to bring the adjacent membrane to threshold causing an action potential in the muscle cell

What is the motor end plate?

Region of the sarcolemma of a muscle fiber (cell) that includes acetylcholine (ACh) receptors, which bind ACh released by synaptic end bulbs of somatic motor neurons. ❑ Junctional folds ❑ Nicotinic cholinergic receptors

What prevents myosin heads from binding?

Regulatory proteins

What are transverse tubules? What is the arrangement?

Small, cylindrical invaginations of the sarcolemma of striated muscle fibers (cells) that conduct muscle action potentials toward the center of the muscle fiber. the transverse tubules dive deep within the muscle cell on either side are parts of the sarcoplasmic reticulum the arrangement is in a triad (includes the sarcoplasmic reticulum reticulum, transverse tubules, and on the other side a sarcoplasmic reticulum) So we have an AP going down the transverse tubules, there are gates on the SR in which are voltage gated (since the AP is the signal traveling down the transverse tubules). The green structure is the sarcoplasmic reticulum, the endpoints (terminals portions of SR) are storehouses for Ca ( aka terminal cisternae on pic).

When looking at the length-tension relationship of a muscle fiber, what is the optimal length?

So at the optimal length (at 100%), we have maximal tension developed; now if we looked at the cross bridges of the actin and myosin the overlap is ideal to get the maximum number of crossbridges forming. At the optimal length you get the maximum number of crossbridges being formed. Optimal length in the muscle creates a optimal length in the sarcomere which creates the max number of cross bridges formed.

Describe the graph of the length-tension relationship of a muscle fiber

So we did frequency of stimulation (fused tetany), here we have the length-tension relationship (length was the sarcomere length and the tension was on the y axiis), and then the 3rd one is muscle fiber diameter (which is just adding more myofibrils and adding more cross bridges). It's all about the number of crossbridges, the more the number of crossbridges the greater the strength. So this would be hypertrophy

What is determined by the number of mitochondria. mypglonin, and glycogen?

TYping and characteristics of the differ types of muscle fibers is determined by the number of mitochondria, myoglobin, glycogen.

What are the 3 ways to make ATP? Which is the fastest?

The 3 ways to make ATP is the creatine phosphate , through glycolysis, or though the aerobic metabolism Out of these 3 creatine phosphate is the fastest way to make ATP (VERY FAST). With glycolysis there 2 steps. With aerobic metabolism theres a lot of steps.

What is oxygen debt? What is Oxygen used for?

The amount of extra oxygen the body needs after exercise to react with the accumulated lactic acid and remove it from the cells ◼ Oxygen consumption remains elevated after the end of exercise (minutes to hours) Whenyou go for a run andwhen you stop your respiration doesn't return to normal immediately since it stays elevated bc you have to pay off the O2 debt. SO that increase in ventilation post exercise is to supply the O2 to pay off the O2 debt. This can last from minutes to hours since the O2 consumption stays up. ❑ Oxygen used for: ▪ Removal of lactic acid by aerobic metabolism So the lactic acid that has been accumulated goes back into the cell and is converted to pyruvic acid and then its burned through aerobic metabolism (which you need O2). ▪ Muscle recovery ▪ Resynthesizing creatine phosphate The muscle recovery is not as clear cut. And creatine phosphate is regenerated. So that all takes time

When does Excitation-contraction coupling occur? What is the excitation?

The excitation is the AP and all the things that occur before you actually get crossbridge cycling, so its what are those events between their arrival of an AP. This mechanism is the stuff before crossbridge cycling.

Explain actin molecules

The individual actin molecules are strung together by beads and there are 2 chains that wrap around each other. On each of these actin molecules is where the myosin head binds. Once the actin is put together, facing outward is all the binding sites for the myosin heads.

What is glucogenesis?

The liver can also undergo this process called gluconeogenesis (-gluc is glucose, -neo means new, -genesis means creation; tThis metabolic process creates new glucose

What are the mjor fuel sources of ATP

The major fuel source is glucose, but fatty acids and amino acids can also be burned to create ATP

What are dystrophines?

The thing that anchors myofibrils to the sarcolemma is dystrophin (blue things), when these contract they pull the whole muscle membrane with it so the whole cell shortens.

What does atrophy do?

Theres no growth in which its an decrease in diameter and this can occur from lack of use The myofibrils are proteins and they're constantly turning over and that turn over rate is going to slow down if they are not stimulated by use so over time the diameter will decrease/atrophy.

What is ATPase?

This is an enzyme that splits ATP to release energy to drive contraction. Atp is broken down by ATPase in which one of its phosphates is removed it becomes ADP, it creates an inorganic phosphate, and releases energy (in which this enregy is used to do something)

What does cooling down do after exercising?

To clean out the whole system after all-out efforts requires a warm down/cool down. If you don't do a cool down you are going to feel heavy limbs the next day and your muscles won't contract; it will get rid of the garbage metabolites that was accumulated during exercise.

Describe and draw the the tension developed by each muscle fiber

Top graph pic (a): Looking at a single muscle fiber; up here we have a single AP and a single muscle twitch (not very useful). ' Lower graph pic (b): Over here we have a single AP we have a muscle twitch; as its relaxing a 2nd AP arrises and it summates; Are the AP summating? No, AP can never summate, but muscle twitches can.

What do troponin and tropomyosin do?

Tropomyosin is the long strand that covers the binding site (Tropomyosin is a long word which represents that its a long strand) Troponin: regulates the position of tropomyosisn;when activated the Troponin molecules pull the tropomyosin revealing the binding site.

What does the NMJ have to do with Excitation-contraction coupling?

We have the neuromuscular junction, all the events come together to create a muscle AP. So the excitation is the NMJ, you need that motor neuron releasing Ach generating a EPP. This then depolarizes the muscle membrane causing a muscle AP, so this is the start we had excitation and now we have all these events before we have crossbridge cycling. So these events are the coupling events between the actual excitation to the crossbridge cycling.

What is the sliding filament mechanism?

When Thin/thick filaments slide past one another thereby shortening the sarcomere as the sarcomere move inward the whole muscle is going to shorten and that is called contraction.

What is motor unit recruitment?

When a muscle needs to generate more force during a contraction, more of its motor units are activated. The process of increasing the number of active motor units is called motor unit recruitment ◼ Small to large motor recruitment ◼ Asynchronous recruitment occurs during submaximal contractions ❑ Delays fatigue

How does a muscle twitch occur?

When an AP travels down here all the muscle fibers that are apart of that motor unit will contract. The response to a single AP down a motor neuron is a single muscle twitch. So this arrow( in pic) is the arrival of the AP and in response we get a muscle twitch.

What is motor unit size?

When we say motor unit size we are referring to the number of muscle fibers within the unit.

Describe the Excitation-contraction coupling in its relaxed states and its main components What is the tropomyosin doing in a relaxed state?

You have the sarcolemma The transverse tubules are deep and they are made up of sarcolemma. So AP travel along the cell membrane just like along axons. The transverse tubules has that triad on either side We have SR (Ca storehouse);Ca is eventually going to be released and to get it back in we have a Ca pump (to pump is back in against its concentration gradient). The blue thing is a voltage gated channel. The green thing is a Ca release channel. At rest, these 2 units are hooked together (the voltage release channel is plugging the Ca release channel) So this is in a relax state, the tropomyosin is blocking the binding sites for the myosin cross bridges.

What is a small motor unit? Where in the body would it be found?

a small motor unit might have 10-20 muscles fibers and One motor neuron You would have small motor units in your fingers (bc you want delicate movements)

What is Dystrophin?

anchors the ends of all the myofilaments anchoring them to proteins embedded in the sarcolemma

What is the skeltal muscle? Why is it called that?

bc its attached to the bone (skeleton); its generally voluntary (in general bc reflexes involve skeletal muscles and they are automatic, its an exception); its striated.

What are the parts of the skeltal muscle fiber

embryonic muscle cells fuse together and develop into a long mature skeletal muscles and the length of muscle cells is the entire length of a muscle nside a muscle cell/fiber (fiber and cell are going to be used interchangeably) are these rod-like structures called myofibrils.

Ex of muscle fatigue with motor unit recruitment What is submaximal and maximal contraction?

if you are holding a pencil and you just need 1 motor unit, if it's only that 1 motor unit being recruited the same muscle fibers contracting, those muscle fibers are going to get fatigued (so they share the load where 1 motor unit works it rests and another motor unit works, etc). So we have a sharing of a load, we don't have the same motor unit being contracted for submaximal contraction. For submaximal contractions we have asynchronous recruitment (not all muscle fibers are contracting at the same time, some are resting and some are contracting, they take turns) For maximal contractions all motor units are recruited (synchronous and its not sustainable since you can't hold a maximal contraction forever bc no motor units get to rest, so fatigue sets in quickly).

What does hypertrophy do?

increase number of myofibrils (not by the number of muscle fibers)

What is fused tetanus?

its a smooth, sustained contraction in which individual twitches cannot be detected and maximum tension is reached. When contracting your biceps it is fused tetanus. Fused tetanus is how we normally have our muscle contracting, we don't have this partial relaxation. There is also a lot more forced (d) generated vs single twitch; fused tetanus 3 or 4 times greater then a single twitch; it is smooth and its muscle tension is greater.

What are myofibrils?

repeating sarcomeres which gives rise to light/dark appearance.

What is rigor mortis?

stiffening of muscles after death the muscles enter a state of rigor (rigidity) mortis (post death) Begins 3-4 hours post-mortem and lasts about 24 hours when a person passes away Ca starts leaking out of sarcoplasmic reticulum. And once it does these are in high energy state and the person is dead, so they can attach, do a power stroke but no new ATP so they cannot detach and so the muscles end in a state of rigor right here (notes) bc no new atp can be made postmortem

What is a triad?

the anatomical arrangement between the terminal cisternae of the SR and T tubules is essential for EC coupling.

What are the contractile proteins?

they generate force during contraction; done by sliding over each other There are 2: Myosin and Actin

How do you prevent atrophy/promote hypertrophy?

you have to contract the muscles Ex: gym in the 90s they hooked up stimulating electrodes to all your muscles and you lay there in which your muscles twitch and contract, this didn't work since there are other things besides n.t.'s released from the neural input (the growth factor things) so it didn't really work.

How do muscles relax? (aka how does ECC go back to resting state)

• Action potentials cease. • Calcium-release channels close • Ca2+ -ATPase pumps Ca2+ back into SR (active transport). • Ca2+ is no longer available to bind to troponin allowing tropomyosin to return to its blocking position on actin.

What are the different periods in a muscle twitch?

◼ Consists of latent (nothing is happening and the muscle is not contracting between the arrival of the AP), contraction, and relaxation periods

What are the 3 types of muscle proteins?

◼ Contractile proteins (myofilaments) ◼ Regulatory proteins ◼ Structural proteins

What is creatine phosphate? How long does it last and when it used?

◼ First source of ATP during muscle contraction (intense all-out efforts) ◼ This is due to the very rapid formation of ATP from creatine phosphate Creatine phosphate donates a phosphate to ADP to make a new ATP. The enzyme that catalyzes it is creatine kinase. the phosphate is up for grabs. ADP is going to grab it and the enzyme that catalyzes it is creatine kinase. We end up with just creatine and ATP. A typical muscle cell has enough creatine phosphate for all-out muscle contraction. This pathway providing ATP lasts 2-10secs.

What is aerobic respiration

◼ Generates ATP when sufficient oxygen is available This is always going on, it's just chugging along constantly. if there's all-out muscular efforts it can't keep up with the demands and that's when anaerobic metabolism and creatine phosphate help out. For all-out efforts it doesn't produce enough ATP and the other 2 mechanisms

What is Anaerobic glycolysis? How long does it last?

◼ Produces ATP when oxygen levels are low This metabolic pathway (anaerobic metabolism ) for all out efforts is 10sec-2 mins of energy that can be provided by anaerobic glycolysis. The greater the effort the less time this pathway will produce ATP.

What is muscle fatigue? What are the reasons for it happening?

◼ The inability of a muscle to maintain force of contraction during a prolonged activity ❑ Reasons ◼ Central fatigue ❑ Associated with the central nervous system (athletes gets tired of exerting/hurting) ◼ Muscle fatigue ❑ Energy availability (we never run out of fat but you need glucose to prime the pump; so if glucose availability goes down (even though there is plenty of fat stored in the body) you will still get fatigued, you need glucose to prime the pump) ❑ Calcium cytoplasmic decline ❑ Oxygen, glycogen, and ACh depletion (thats central fatigue) ❑ Lactic acid buildup

What is included in cross-bridge cycling?

❑ A single power stroke moves filament only a small percentage. When a sarcomere shortens, there are a series of power strokes. This is called cross-bridge cycle. A single power stroke move the thin filament only a small amount so you need a whole series of power strokes for meaningful contraction. ❑ Asynchronous cycling occurs to prevent slippage of filaments between power strokes. Some myosin heads are always in contact with actin filaments The myosin heads do Asynchronous cycling. so there's always some heads attached while others are releasing (asynchronous)

What are the types of atrophy?

❑ Disuse atrophy - loss of myofibrils ❑ Denervation atrophy - loss of myofibrils which are slowly replaced connective tissue Its the loss of nerve (removal of nerve innervation and without that the muscles atrophy Without the nervous input in addition to the n.t. 's there are growth factors that maintain the muscle cell and without those the muscle cells are slowly replaced with connective tissue.

What is an end plate potential?

❑ Large graded potential ❑ Always excitatory ❑ Travels to adjacent sarcolemma ❑ Single EPP can bring the membrane to threshold to fire an A

Gradation of Whole Muscle Tension/ Force of muscle contraction is determined by what?

❑ Tension developed by each muscle fiber 1. Frequency of stimulation (tetany) 2. Muscle fiber length (length-tension relationship) 3. Muscle fiber diameter ❑ Motor Units 1. Motor unit size 2. Motor unit recruitment 3. Muscle fiber type Single muscle twitch isn't very useful so we're gonna put it together into the gradation of whole muscle tension (not of a single muscle twitch).