Lecture 4: Muscle Physiology for Skeletal Muscle Flashcards
Striated vs Smooth Muscle
Striated: actin and myosin are highly organized in sarcomeres
Smooth: actin and myosin are diffusely organized in the cell
What is “Excitation Contraction Coupling”?
Excitation Contraction Coupling is the process by which an outside signal is translated into activation of a muscle cell. The mechanism of EC coupling is very different btw cardiac and skeleta.
Skeletal muscle is composed of bundles of muscle fibers: each such bundle is called a ______. A muscle fiber represents an individual muscle cell and contains bundles of _____. The striations are due to the arrangement of ______.
Skeletal muscle is composed of bundles of muscle fibers. Each such bundle is called a fasiculus. A muscle fibers represents an individual muscle cell and contains bundles of myofibrils. The striations are due to the arrangement of thick and thin filaments.
Draw a sarcomere. Show and name each section: sarcomere, Z line, A band, H band, M line, thin vs thick filaments.
Name each part of this diagram
When a muscle contracts, which bands shorten?
The I bands shorten (containing only thin filaments aka actin)
The H band shorten (the area where there is only thick bands/myosin)
A BANDS STAY THE SAME (myosin end to myosin end which has thin and thick filament overlap)
What exists at the end of the muscle and how does its structure help attach it to bone?
The end of muscle is collagen. There is interdigitation between collagen and bone: muscle and collagen overlap to give a lot of surface area.
Myofibrils are surrounded by______
SR
Collagen is also connected through the ______ and attached to various _______. Musclar dystrophy is….
Collagen is connected to integrin proteins and those connections go through the cell membrane. A protein called dystrophin helps with connected structural proteins outside and inside the cell. In musclar dystrophy, your dystrophin doesn’t work right, so the connections aren’t great, when muscles contract they tear the cell membrane, muscles eventually die off.
A thick filament is formed by the polymerization of _____ in a tail to tail configuration extending from the center of the ____. How many myosin heads per myosin?
Thick filament is made from MYOSIN, extending from center of sarcomere. Two myosin heads
Explain how a neuromuscular junction works.
Nerve goes really close to the motor end plate/muscle. AP travels down the axon and when it gets to the end and depolarizes the presynaptic terminal, it triggers calcium to come into that space, triggering vessicles carrying ACh to fuse to the membrane. Those vessicles leave via exocytosis and enter the synaptic cleft. The ACh binds to ligand gated channels, which then allow sodium and potassium, channels to both open. Na will come in and K will go out, both actions depolarize the cell. If the depolarization is big enough, it reaches threshold and you can get an AP in muscle fiber.
When an AP then gets fired into a muscle cell, explain the EC coupling cascade that happens at the sarcolema in SKELETAL MUSCLE.
Stimulation of muscle fiber initiates an AP in the muscle that travels down the T tubule. Within the T tubule there are “voltage sensors” aka DHPR sensors that tug on RYR receptors that are attached to the SR. IMPORTANT to note that nothing crosses over between tubule and SR, it’s “mechanistic coupling.” Once RYR gets pulled, calcium is released into the cytosol by the SR. Increased calcium can then cause a contraction. When the muscle is ready to relax, SERCA uses ATP to pump it back into the SR for storage.
Explain the timing of the following in skeletal muscle: Increased CA, AP, and Twitch Force.
Series of Events:
AP causes increased Ca which then causes a twitch force
So AP causes increase calcium which causes increase in force (check the graph)
Explain the “triad”
Within the T-tubule of skeletal muscle, DHPRs are clustered at the triad junctions where they make physical contact with the RyR on the SR membrane.
There are four DHPRs for every one RyR.
What is calsequestrin?
What is SERCA
Calsequestrin is a low affinity calcium binding protein that helps accumulate ca++ in the terminal cisternae. It acts as a calcium buffer in the SR.
SERCA is a ATPase transporter that binds calcium and puts it back into the SR when the muscle relaxes.
Explain the mechanism by which calcium allows muscles to contract.
Calcium binds troponin C, and by binding at that site, tropomyosin moves out of the way for myosin to then interact with actin.
“The contractile force of skeletal muscle increases in a calcium dependent manner as a result of binding of calcium to troponin C and the subsequent movement of tropomyosin away from myosin binding sites on underlying actin molecules.”
Graph shows force as a function of calcium concentration inside the cell
Draw the length-tension graph for skeletal muscle. Describe why it has the shape that it does.
Stress as a function of length
To the left of plateau: force is lower because thin filaments are running into each other
Plateau: optimal amounts of thick and thin filament overlap– maximum functioning of cross bridges
Right of plateau: not enough myosin heads can grab onto the actin, eventually there is no overlap and no tension
The passive curve exists because the muscle fibers have a natural elasticity to them
Draw the force velocity curve for skeletal muscle and describe why it has the shape that it does.
This curve is basically about how fast you can move a muscle. The black curve is the “velocity stress curve”. Basucally, at Vo there is a maximum velocity in which muscle can shorten (how fast myosin can go). As you increase the load (stress), the muscle goes slower and slower. There is an inverse relationship between velocity and load. There reaches a certain point where your muscle cannot move a load because it is too heavy (x intercept). Super heavy loads, you cannot give enough force to cancel out gravity and your muscles lengthen.
Power curve: as super light loads you aren’t doing much work (low power), the sweet spot is in the middle of the power curve it looks like an arch. There is a certain point where power maxes out.
Explain what the sympathetic stimulaton of the heart does and the cascade it creates within the cytosol.
So E/NE binds, which causes G protein coupled cascade. cAMP levels rise, which activates PKA. PKA then goes and phosphorylates the L-type calcium channel, the RyR receptor, PLN, and troponin.
The concequences of the phosphorylation are:
L type channel lets more Ca come in
RyR has more current, which lets more CA out of SR
PLN can no longer inhibit/slow down SERCA, so more calcium gets put back into the SR
Troponin’s affinity for Calcium DECREASES (this is important because it allows the cardiac muscles to release calcium and relax)
