4a. Skeletal Muscle and Neuromuscular Junction (NMJ) Flashcards
motor unit
motor neuron and all the fibers that it innervates
direct innervation (no ganglia)
motor end plates
located at skeletal muscle membrane
synapse with motor nerve terminal
motor neuron site of action potential
axon hillock
tetrodotoxin
blocks Na+ channel
botulinum toxiun
cleaves SNARE proteins
decrease NT release
physostigmine/neostigmine
blocks AChE
increases ACh at NMJ
curare
(d-tubocurarine)
competitive antagonist for ACh to bind to the AChR
less ACh able to bind
=muscle relaxant
end plate potential
graded potential (20mV)
generated by stimulation causing a change in membrane potential
almost always triggers AP
dihydropyridine receptor (DHPR)
functions as a voltage sensor in skeletal muscle
triggers intracellular Ca++ release from SR
T- tubules inside charge
+
T-tubules outside charge
-
t tubules function
conduct AP into interior muscle fibers
DHPRs activated by AP
results in physical contact w/RyR to release Ca++
Calcium-Induced Calcium Release
(CICR)
Ca++ release by the action of Ca++ alone without simultaneous action of other activating processes
Primary mechanism of Ca++ release
- direct protein-protein interaction between the DHPR and RyR
Ryanodine Receptor
responsible for Ca++ release from SR
when DHPR connects w/RyR
Ca++ is released
Excitation-Contraction Coupling
DHPR connecting w/RyR to facilitate Ca++ release
increase intracellular Ca++
myosin head
attaches to actin
power stroke (hydrolysis products released)
binds to new ATP
detaches from actin
myosin chains
heavy chain
light chain (regulatory)
Actin filaments
provide cells w/mechanical support and driving forces for movment
Troponin C (TnC)
Ca++ binding subunit
(during excitation)
Troponin
works w/tropomyosin to unblock active sites between myosin and actin
allows cross-bridge cycling
contraction of myofibrils for systole
Tropomyosin
binds w/troponin to help position it on the actin molecule
prevents myosin from forming cross-bridges while in a resting state
actin
protein that interacts with myosin filaments to generate tension
Hydrolysis of ATP/Power Stroke
- ATP binds to myosin head (Attached)
- dissociation of actin-myosin complex for myosin to bind to ATP (RELEASED) - ATP is hydrolyzed
- myosin heads return to resting conformation - cross-bridge forms
- myosin head binds to new action position - Phosphate release
- power stroke: filaments slide past each other - ADP released
During muscle contraction, what happens to the H zones and I/A bands
H zones shrink/narrow
I band shrink/narrow
A band does not change
sarcomere optimal overlap
produces optimal force
too much overlap
lower force
not enough overlap
lower force
AChE breaks down ACh into
Choline + Acetic Acid
choline acetyltransferase (ChAT)
converts choline and acetyl CoA into ACh
3 ways to terminate contraction-reuptake of Calcium
- NCX (Na/Ca exchanger)
- SERCA
- Calsequestrin
Na+/Ca++ exchanger
secondary active transporter
requires ATP
pumps one ion down gradient and the other up gradient
Sarcoendoplasmic Reticulum Calcium ATPase (SERCA)
pump transports Ca++ from cytosol back into SR against concentration gradient after muscle contraction
primary active transport
requires ATP
Calsequestrin
major Ca++ binding protein in SR
main Ca++ storage
regulator of Ca++ release channels in skeletal/cardiac muscle
fiber summation
recruit additional motor units
frequency summation
of individual fibers
unfused tetanus
muscle fibers do not completely relax before next stimulus b/c they are being stimulated at at fast rate
Ca++ not at highest level (can trigger more Ca++ release from SR)
partial relaxation between twitches
(partial summation)
fused tetanus
complete tetanus
no relaxation period between muscle contractions
Ca++ reached highest level (cannot trigger more Ca++ release from SR)
(full summation)
muscle relaxants
depolarizing
non depolarizing
depolarizing agent
succinylcholine
(partial agonist)
succinylcholine mechanism
activates NAChR
maintains depolarization (keep open)
causes paralysis
- muscle fatigue
- ion conc gradient?
stops breathing
non-depolarizing agent
d-tubocurarine
(antagonist)
d-tubocurarine mechanism
blocks binding of receptor
ACh cannot bind
No conformational change of receptor
No EPP
No AP
Rhabdomyolysis
damaged muscle tissue releases its proteins and electrolytes into the blood
Rhabdo symptoms
reddish/brown urine
muscle pain/weakness/fatigue
Rhabdo blood serum
high creatine kinase
high potassium
high myoglobin
low Ca++
Rhabdo kidney damage
myoglobin is filtered out by the kidneys which causes damage to the kidneys
Myasthenia Gravis
autoimmune diease
antibodies bind to nAChR
weakening skeletal muscles
