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 differences between skeletal and caridac muscle E-C coupling.
Skeletal Muscle: calcium “voltage” channels (DHPR’s in T tubular membrane physically link to the RyR. Depolarization of T tubule changes the DHPR, which undergoes a conformational change and tugs on the RyR, causing the RyR on the SR to open and release calcium. Repolarization moves the T tubular channel back, and shuts off SR Ca2+ release. Skeletal muscle EC is mechanically coupled, and called voltage dependent Ca-release (VDCR)
Cardiac: In the heart, Ca2+ actually crosses the DHPR and binds to the RyR, triggering the release of calcium in the SR. Calcium entry is ESSENTIAL and required to trigger SR calcium release. More calcium influx triggers more SR Ca release. NOTE: this is called Calcium Induced Calcium Release (CICR). This process is stopped when RyR inactivates.
If you put both skeletal muscle and cardiac muscle in solutions containing NO calcium ions, what happens?
Without the presence of calcium, skeletal muscle can still contract.
CARDIAC MUSCLE CANNOT CONTRACT without calcium (they take advantage of this in heart surgery)
Explain the interaction btwn PLN and SERCA.
Phospholambdin (PLN) is an inhibitor of SERCA (it slows it down). PLN is bound on the side of the SERCA pump. PLN is important, because when it gets phosphorylated in the presence of adrenaline, it stops inhibiting SERCA, and the heart can contract more vigorously during exercise.
Again, when adrenaline is present, PLN is phosphorlayted and can no longer slow down SERCA.
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
What happens during rigor mortis?
During rigor mortis, there is an absence of ATP. Actin gets stuck to myosin…. muscles get struck and the filaments can’t slide anymore.
Myosin needs to bind ATP to release from actin, when there is no more ATP left, myosin gets stuck to actin.
Compare and contrast the Type I vs Type II muscles in the various categories:
ATPase rate for myosin
SR calcium pumping capacity
Diameter
Oxydative capacity (mitochondria, capillary, myoglobin)
Glycolytic Capacity
Type I: “slow oxidative”
- slow ATPase rate for myosin
- moderate SR calcium pumping capacity
- moderate diameter
- High oxidative capacity
- Moderate Glyolytic capacity
Type II: “Fast glycolytic”
- Fast myosin ATPase rate
- High SR calcium pumping capacity
- large diameters
- low oxidative capacity
- High glycolytic capacity
For type II muscles
cell diameter
conduction velocity
excitability
number of fibers
contraction velocity
fatigability
Type II is FAST GLYCOLYTIC
Large cell diameter
Fast conduction velocity
LOW excitability
many fibers
fast contraction velocity
HIGH fatigability
For Type I muscles:
cell diameter
conduction velocity
excitability
number of fibers
force of unit
contraction velociuty
fatigability
Type I: Slow oxidative muscles
small cell diameter
low conduction velocity
high excitability
few fibers
small force
moderate conduction velocity
low fatigability
Which kind of muscles are typically recruited first?
Slow muscles
