Review of Skeletal Muscle Physiology - Montemayor

Question 1

40yo M perioral numbness

• ate puffer fish
• muscle weakness
• respiratory and speech involvement
• IV hydration, intubation, sedation, activated charcoal

toxin?

Answer 1

tetrodotoxin (TTX)
-no specific lab - diagnosis on dietary history

activated charcoal binds toxin

Question 2

MOA tetrodotoxin

Answer 2

blocks voltage gated Na channels**

depolarization is inhibited
-AP generation and propagation is inhibited

Question 3

change most rapidly hypopolarize the RMP

Answer 3

blockage of K leak channels

Question 4

dendrotoxin

Answer 4

from mamba snakes

Question 5

dendrotoxin MOA

Answer 5

blocks voltage gated K channels

inhibits repolarization phase

Question 6

dendrotoxin on ACh release at NMJ

Answer 6

inhibits repolarization
-prolongs the action potential

ACh release requires Ca - due to AP

so have prolonged Ca influx
-increased ACh release**

hyperexcitability and convulsion

Question 7

5yo M dental clinic

• general anesthesia
• halothane mask induction
• temp rises, muscle rigidity, tachycardia, elevated PCO2
• admitted to hospital

Answer 7

malignant hyperthermia

Question 8

malignant hyperthermia

Answer 8

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

Question 9

mutation in malignant hyperthermia

Answer 9

RYR1

Question 10

ryanodine receptor

Answer 10

SR membrane

Ca release channel

Question 11

DHPR receptor

Answer 11

dihydropyridine receptor
-L-type Ca channel

located T tubules

Question 12

DHPR MOA

Answer 12

voltage sensor

-detect presence of arriving depolarization

Question 13

Ca in skeletal muscle

Answer 13

binds troponin C

• remove tropomyosin from actin
• cross bridges form

Question 14

number of cross bridges

Answer 14

proportional to tension created

Question 15

muscle relaxation

Answer 15

need ATP
-to unbind actin and myosin

also to remove Ca from sarcoplasm

Question 16

SERCA

Answer 16

sarcomplasmic and endoplasmic reticulum Ca ATPase

primary pump for removing Ca from sarcoplasm in order for relaxation of skeletal muscle to occur

Question 17

most important mechanism for returning Ca to resting levels in skeletal m

Answer 17

SERCA pump

on SR - reuptake

Question 18

27yo F enlarged thymus

• difficulty reading
• diplopia
• blurry vision
• muscle weakness
• Abs against nicotinic ACh receptor in plasma

Answer 18

myasthenia gravis

Question 19

myasthenia gravis

Answer 19

get worse throughout day

and improve with rest**

extraocular muscles first affected

also bulbar, neck, prox limb muscles

Question 20

Ab against nAChR

Answer 20

myastenia gravis

Question 21

end plate potential in myasthenia gravis

Answer 21

absent

fewer channels able to open
-decreased ability to generate end plate potential

Question 22

ACh binding nAChR in skeletal muscle at motor end plate

Answer 22

opening of ligand gated cation channels and depolarization of end plate to Vm between Na and K equilibrium

Question 23

end plate potential

Answer 23

opening of nAChR channel at motor end plate

Question 24

nACh receptor

Answer 24

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)

Question 25

effect of end plate potential on adjacent sarcolemma of skeletal m fiber

Answer 25

threshold reached

• voltage Na open
• muscle AP generated

Question 26

enzyme terminates neurotransmitter activity at NMJ

Answer 26

acetylcholinesterase

Question 27

enzyme catalyzes formation of ACh

Answer 27

choline acetyltransferase

choline + acetyl CoA

Question 28

drives ACh uptake into vesicle

Answer 28

proton gradient
-positive voltage and low pH inside

ACh/H exchanger - inward ACh to outward H+

Question 29

tensilon test

Answer 29

diagnosis of myasthenia gravis

acetylcholinesterase inhibitor
-prolongs presence of ACh at synaptic cleft

Question 30

ice pack test

Answer 30

cooling slows the AChE activity

can cause temporary improvement of ptosis

Question 31

myasthenia gravis and eyes

Answer 31

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

Question 32

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

Answer 32

lambert eaton myasthenic syndrome

-paraneoplastic - with small cell lung ca

Question 33

lambert eaton myasthenic syndrome

Answer 33

pre-synaptic disorder

autoimmune attack at voltage gated Ca channels motor nerve terminal

Question 34

Ca influx at neuromuscular junction

Answer 34

ACh vesicle fusion and exocytosis

Question 35

vesicle protein Ca sensor

Answer 35

synaptotagmin

Question 36

increased muscle strength with stimulation

Answer 36

lambert eaton

more stimulation - more Ca influx via functioning channels

Question 37

decreased muscle strength with stimulation

Answer 37

myasthenia gravis

Question 38

omega conotoxin

Answer 38

blocks N-type voltage gated Ca channels

marine cone snail venom

like lambert eaton effect

Question 39

40yo F dry mouth, double vision, difficulty swallowing and speaking
-c. botulinum infection

Answer 39

botulism

-flaccid paralysis

Question 40

MOA of botulinum toxin

Answer 40

impaired ACh vesicle fusion

B, D, F, G - synaptobrevin (v SNARE)
A/E - SNAP-25 (t SNARE)
C1 - syntaxin

Question 41

10yo M jaw pain

• difficulty swallowing
• worsened
• stepped on metal

Answer 41

tetanus

Question 42

tetanus

Answer 42

neurotoxin of clostridium tetani

Question 43

spastic paralysis with tetanus toxin?

Answer 43

effect on synaptobrevin

-tetanus - impact spinal inhibitory interneurons

Question 44

inhibitory interneurons

Answer 44

tetanus

Question 45

motor end plate

Answer 45

botulinum