Muscle - Schuschke Flashcards
(43 cards)
(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.
