Review of Skeletal Muscle Physiology - Montemayor Flashcards
40yo M perioral numbness
- ate puffer fish
- muscle weakness
- respiratory and speech involvement
- IV hydration, intubation, sedation, activated charcoal
toxin?
tetrodotoxin (TTX)
-no specific lab - diagnosis on dietary history
activated charcoal binds toxin
MOA tetrodotoxin
blocks voltage gated Na channels**
depolarization is inhibited
-AP generation and propagation is inhibited
change most rapidly hypopolarize the RMP
blockage of K leak channels
dendrotoxin
from mamba snakes
dendrotoxin MOA
blocks voltage gated K channels
inhibits repolarization phase
dendrotoxin on ACh release at NMJ
inhibits repolarization
-prolongs the action potential
ACh release requires Ca - due to AP
so have prolonged Ca influx
-increased ACh release**
hyperexcitability and convulsion
5yo M dental clinic
- general anesthesia
- halothane mask induction
- temp rises, muscle rigidity, tachycardia, elevated PCO2
- admitted to hospital
malignant hyperthermia
malignant hyperthermia
rare, heritable
- auto dom
- triggered by anesthetics and muscle relaxants
mutated ryanodine receptor
- disorder of Ca regulation
- uncontrolled release of Ca from SR
rigidity, tachycardia, hyperventilation, hyperthermia
acute hypermetabolic state - prolonged contraction of muscle
mutation in malignant hyperthermia
RYR1
ryanodine receptor
SR membrane
Ca release channel
DHPR receptor
dihydropyridine receptor
-L-type Ca channel
located T tubules
DHPR MOA
voltage sensor
-detect presence of arriving depolarization
Ca in skeletal muscle
binds troponin C
- remove tropomyosin from actin
- cross bridges form
number of cross bridges
proportional to tension created
muscle relaxation
need ATP
-to unbind actin and myosin
also to remove Ca from sarcoplasm
SERCA
sarcomplasmic and endoplasmic reticulum Ca ATPase
primary pump for removing Ca from sarcoplasm in order for relaxation of skeletal muscle to occur
most important mechanism for returning Ca to resting levels in skeletal m
SERCA pump
on SR - reuptake
27yo F enlarged thymus
- difficulty reading
- diplopia
- blurry vision
- muscle weakness
- Abs against nicotinic ACh receptor in plasma
myasthenia gravis
myasthenia gravis
get worse throughout day
and improve with rest**
extraocular muscles first affected
also bulbar, neck, prox limb muscles
Ab against nAChR
myastenia gravis
end plate potential in myasthenia gravis
absent
fewer channels able to open
-decreased ability to generate end plate potential
ACh binding nAChR in skeletal muscle at motor end plate
opening of ligand gated cation channels and depolarization of end plate to Vm between Na and K equilibrium
end plate potential
opening of nAChR channel at motor end plate
nACh receptor
permeable to cations
Na and K become equally permeable
-relative increase in Na permeability
Vm shifts to value between E-K (-80) and E-Na (+50)
effect of end plate potential on adjacent sarcolemma of skeletal m fiber
threshold reached
- voltage Na open
- muscle AP generated
enzyme terminates neurotransmitter activity at NMJ
acetylcholinesterase
enzyme catalyzes formation of ACh
choline acetyltransferase
choline + acetyl CoA
drives ACh uptake into vesicle
proton gradient
-positive voltage and low pH inside
ACh/H exchanger - inward ACh to outward H+
tensilon test
diagnosis of myasthenia gravis
acetylcholinesterase inhibitor
-prolongs presence of ACh at synaptic cleft
ice pack test
cooling slows the AChE activity
can cause temporary improvement of ptosis
myasthenia gravis and eyes
notice eye issues easier
- less synaptic folds - fewer AChR to begin with
- higher rate of firing frequency of ocular motor neurons
lower release of ACh vesicles per synaptic event
43yo M small cell lung carcinoma
- proximal muscle weakness
- absent DTRs
- EMG - low amplitude muscle response with increase after repeated activation
- Abs against voltage gated Ca channels detected
lambert eaton myasthenic syndrome
-paraneoplastic - with small cell lung ca
lambert eaton myasthenic syndrome
pre-synaptic disorder
autoimmune attack at voltage gated Ca channels motor nerve terminal
Ca influx at neuromuscular junction
ACh vesicle fusion and exocytosis
vesicle protein Ca sensor
synaptotagmin
increased muscle strength with stimulation
lambert eaton
more stimulation - more Ca influx via functioning channels
decreased muscle strength with stimulation
myasthenia gravis
omega conotoxin
blocks N-type voltage gated Ca channels
marine cone snail venom
like lambert eaton effect
40yo F dry mouth, double vision, difficulty swallowing and speaking
-c. botulinum infection
botulism
-flaccid paralysis
MOA of botulinum toxin
impaired ACh vesicle fusion
B, D, F, G - synaptobrevin (v SNARE)
A/E - SNAP-25 (t SNARE)
C1 - syntaxin
10yo M jaw pain
- difficulty swallowing
- worsened
- stepped on metal
tetanus
tetanus
neurotoxin of clostridium tetani
spastic paralysis with tetanus toxin?
effect on synaptobrevin
-tetanus - impact spinal inhibitory interneurons
inhibitory interneurons
tetanus
motor end plate
botulinum
