Muscle - Schuschke Flashcards
(3) features which ensure neuromuscular transmission
1) More Ach is released than is necessary to depolarize the motor end-plate
2) the post-junctional membrane contains more Ach receptors than necessary
3) The EPP (end-plate potential) magnitude is 3-4 times that required to initiate depolarization of the sarcolemma
What is the MEPP? What is the result?
miniature end-plate potential. Occurs when the muscle is relaxed, small amounts of Ach are still dripping on the motor end-plate, basically to keep it awake.
This means the motor end-plate (of the muscle) does not have a stable resting membrane potential, but rather there are constant small variations (see graph with shaky lines, slide 5)
TTX blocks the voltage-gated Na+ channels, resulting in?
Action potential will be prevented from starting
Dendrotoxin (from Black Mamba) blocks voltage-gated K+ channels, resulting in?
Prevention of repolarization of the presynaptic membrane = repolarization paralysis. This will prolong the duration of the AP and facilitate release of Ach.
If botox prevents the release of Ach, what kind of neuromuscular blockage is this?
non-DEpolarizing
Physostigmine functions to block Acetylcholinesterase, what kind of neuromuscular blockage is this?
if you don’t remove the Ach, you can’t reset the EPP, can’t get another EPP and can’t stimulate Na channels again. Thus, it is non-DEpolarizing after a short period of time.
Succinylcholine is a short-term paralytic that can be used to paralyze respiratory muscles for intubation. It works as an AchR (receptor) agonist that is not metabolized by AchE. What kind of neuromuscular blockage is this?
causes prolonged depolarization, which leads to a flaccid paralysis as Na+ channels near the end-plate become inactive
Myasthenia Gravis has antibodies that take out the Ach Receptors. What is the effect? How do you combat this?
muscle weakness. Combat it by inhibiting AchE, so that atleast the receptors that are left are getting Ach and getting opened. This is the best chance for getting an AP.
Why does a motor neuron have a hyperpolarization (overshoot) period but a skeletal fiber does not?
Because there is a lot more surface area of a skeletal muscle (think about all the T-tubule invaginations) v. surface area of nerve membrane.
What does the T-tubule contain? Where does a T-tubule lie? Why is this important?
contains extracellular fluid. That means T-tubule is high in Na+ and Ca+ and LOW in K+.
Lies right on top of overlap of actin and myosin = right where contraction is going to occur. So if you depolarize the T-tubules, will allow Ca+ to be released and getting contraction = Excitation-Contraction Coupling.
What are dihydropyridine receptors and where are they found? What and where are Ryanodine receptors?
Dihydropyridine receptors are L-type voltage-gated Ca++ channels. “L” = long-acting. [Voltage-gated = change in polarity required to open them.] Located in T-tubules.
Ryanodine receptors = Ca++ release channels in the SR membrane. These are NOT voltage-gated! So a little of cytoplasm is between the Dihydropyridine and Ryanodine receptors.
What are 3 differences regarding dihydropyridine receptor (DHPR) and ryanodine receptors in skeletal muscle v. cardiac muscle?
- In skeletal muscle, every DHPR is strictly associated with a Ryanodine receptor. NOT the case in cardiac, where they may or may not be associated w/ Ryhanodine.
- In skeletal m., there are NO DHPRs in the sarcolemma. Whereas, cardiac does have DHPRs in sarcolemma.
- Different isoforms of DHPRs, so not affected by the same blockers. Ex. can use Ca++ channel blocker to improve heart function and NOT affect skeletal muscle
[Also, Cardiac has Dyad (less extensive) and skeletal has Triad]
Ca++ channel induced Ca++ release
ONLY is dependent on voltage-induced conformational change in dihydropyridine, which is an L-type Ca channel. In skeletal m, Ca++ does NOT have to go through it; only requires a conformational change.
Ca++-induced Ca++ release
in cardiac muscle, REQUIRES Ca++ to activate the RYR(unlike skeletal muscle, which only requires conformational change of DHPR). So you need about 20% of your Ca++ coming from outside the cell, then the rest of it comes out of cell. Once get some Ca++, starts a cascading effect opening more and more RYRs that release more Ca++
Troponin C is associated with what? Not found where?
associated with thin filaments. It’s job is to bind Ca++ to the thin filaments in skeletal and cardiac.
NOT found in smooth muscle
Calmodulin does not affect which muscle? What does it do in the other two muscles.
does not affect in skeletal muscle. In cardiac m, Calmodulin is a modulator. In smooth m, it’s a requisite! Ca-Calmodulin complex activates a Myosin Light Chain Kinase (MLCK), which causes a phosphorylation of one of the regulatory proteins. When you do this in cardiac muscle, it improves contraction = better. In smooth muscle, if you don’t phosphorylate the regulatory light chain, you do not get contraction.
Structure of a myosin molecule
Each myosin molecule has 2 heavy chains (divided into tail, arm (hinge), and a double head. The heads form complexes with 2 light chains:
- Alkili light chain stabilizees the head
- Regulatory light chain regulates ATPase activity by being phosphorylated. ATPase (which hydrolyzes ATP to get energy for contraction to occur) is adjacent to this chain.
At rest, what is associated with myosin head?
At rest, the myosin head is associated with ADP + Pi AND has hydrolyzed ATP to get to that point, which means it’s associated with energy, but cannot interact with myosin (due to Tropomyosin being in way). Thus, myosin is all ready to go = ‘high-affinity myosin”! As soon as active sites uncovered, myosin will bind and shortening will occur.
What happens during the power stroke?
When the actinomyosin complex forms, the ADP + Pi molecules are released from the myosin head. The myosin head utilizes the energy from hydrolyzing ATP earlier to pull the actin filaments towards the center of the sarcomere.
SERCA in skeletal v. cardiac muscle
Smooth endoplasmic reticulum Ca pump (SERCA). Is an ATPase located in SR that pumps Ca against its gradient. It is always running. As soon as you dump the Ca+ out of the SR, you start pumping it back in with SERCA.
- In skeletal m, does not have phospholamban and does not have a second sarcolemma pump.
- SERCA ATPase does resequeter Ca back into cardiac muscle cell. BUT since cardiac muscle requires that 20% of its (starter) Ca come from outside the cell, can’t pump all the Ca back in. So plasma membrane Ca+ pump (also an ATPase) in the SARCOLEMMA pumps Ca+ out of the cell. Also, phospholamban can make cardiac SERCA run faster.
phospholamban
only seen in cardiac m, and NOT skeletal. If phosphorylated, can make the SERCA pump run faster. So if contracting heart faster, will want to relax it faster.
Reduced activity of SERCA Ca++ pump could cause what symptom?
Muscle stiffness after exercise with slower and longer contractions
Regulation of striated v. smooth muscle contraction.
Smooth m is “thick filament regulated.” free Ca++ complexes with Calmodulin. The Ca-calmodulin activates MLCK. MLCK phosphorylates regulatory light chain of the myosin head, which allows the actin myosin cross-bridge. THUS, calmodulin and NOT TnC is the Ca++ binding protein that regulates contraction.
Striated muscle is “thin filament regulated”
(3) things that must occur in order for smooth muscle to relax
1) Ca++ must be sequestered (removed) to ECF
2) MLCK inactivated (dephosphorylated) by cAMP
3) myosin light chain (MLC) dephosphorylated by the Myosin Light chain Phosphatase.
As opposed to striated, where all you need to do is decrease Ca.
How do nitrovasodilators like nitroglycerin (for chest pain) work?
MLC (myosin light chain) v. Myosin phosphatase: whichever is present in greater abundance will give you the contraction or the relaxation.
Nitroglycerin donates nitric oxide, which promotes activity of myosin phosphatase. This dephosphorylates the regulatory light chain, causing relaxation of vascular smooth muscle!
all or none response in muscles
the all or none muscle twitch applies to each cell individually. The entire muscle contraction is not on an all or nothing response.
What is isometric contraction? What force does it have?
‘iso’ = same and ‘metric’ = length. Thus, muscle length does not shorten. Muscle ends are held at fixed points. But there is a contraction (i.e. sarcomere shortening). Also generates a MAXIMAL force.
length-tension relationship
the amount of stretch on a sarcomere will affect the amount of force that muscle can generate. There is an optimal length where all the myosin heads are interacting with actin in between too short and too stretched out. Skeletal muscle keeps muscles attached right at that optimal length. Not the case with cardiac muscle.
Describe isotonic contraction. What happens during shortening of the muscle?
‘iso’ = same, ‘tonic’ = tension. This occurs when one end of the muscle is free to move. At first, the muscle will contract isometrically (developing force w/out contracting) until it generates MORE tension than the load imposed on it. Once the muscle has generated more than the load, it will shorten.
*During shortening, the muscle’s tension remains constant. So the force (tension) is constant during the isotonic phase.
What happens if the load imposed on a muscle exceeds the capacity of the muscle to generate tension?
the muscle will ONLY contract isometrically
Isometric v. isotonic. Which generates more force? Which does more work?
isometric generates more force than isotonic.
W = F x d. (Work = force x distance) Isometric is not moving any distance, so it’s not doing any work. Thus, isotonic does more work. But isometric generates more force.
What’s the rate-limiting factor in the cross-bridge cycle?
hydrolysis of ATP determines how fast you go through this cycle of muscle shortening
Why does increased weight change the rate of the cross-bridge cycle?
ATP hydrolysis by ATPase is the rate-determining factor of this cycle. But the greater the weight load, the slower ATP hydrolysis reaction, which will slow time to go around cross-bridge cycle and, thus, slow down contraction.
How is the number of muscle cells associated a motor unit important?
motor units with very few muscle cells associated with it (~100) have very low thresholds. Motor units with thousands of muscle cells associated with it have HIGH thresholds. On a gradation response.
To move a heavy load, will need a bigger stimulus intensity because you are recruiting bigger motor units.
synchronous v. asynchronous summation
Synchronous is where all muscles are firing at same time and you get one very large muscle twitch or contraction.
Asynchronous: get motor units firing at altering times to maintain tension over long periods of time. BUT there is always the same number of motor units firing and force is maintained.
Ex. Standing up to lecture, the muscles in legs and back must maintain a constant tension. Requires asynchronous firing. Because if same motor unit was continuously firing, it would fatigue quickly.
What is temporal summation. Why does it happen?
if you don’t allow a muscle to completely relax and give it another AP before the Ca transient has decreased or before force has returned back to baseline, you can have an additive effect and get summation.
If you hit it again, can add to it even more. Etc.
Temporal summation happens because you don’t allow the stretch to be in the system (keep elastic element out of it) and then have a greater Ca transient.
What is red muscle fiber? Name (5) characteristics of it. Example?
Red muscle = slow twitch, efficient, and harder to fatigue. (Dark meat on turkey is in legs).
- High amounts of myoglobin
- Lots of mitochondria
- Slow myosin ATPase isoform
- Slow SERCA pump
- Dense capillary network
Ex. Soleus (anti-gravity muscles) are slow twitch.
What is white muscle fiber? Name (4) characteristics of it. Example?
White = fast twitch.
- Low myoglobin (anaerobic respiration)
- Few mitochondria (anaerobic respiration)
- Fast myosin ATPase isoform
- Fast SERCA
Ex. fast ocular muscles = quick twitch and fatigueable
Dilated heart v. hypertrophied heart
hypertrophied heart = diastolic heart failure. Means the wall is thicker and less compliant, so can’t fill it as well, but can empty it fine.
dilated heart = systolic heart failure. Overfill the heart, but problem is with emptying it.
If you’re in a case for 6 weeks, do you diminish the amount of muscle cells?
No. The cells are still there, but the contractile structures have changed. Muscle has atrophied, but can be rebuilt. So, # of cells have not changed.
What is the optimal length of a sarcomere?
2-2.2 micrometers
What would destruction of calsequestrin cause?
Decreased rate of skeletal and myocardial relaxation. B/c Calsequestrin takes Ca in SR and takes it out of the [ ] gradient, so SERCA pump will have to work harder if calsequestrin is not there.
What would destruction of myosin light chain kinase cause?
inhibition of the actin-myosin interaction in smooth muscle
