lecture 19 + 20

Question 1

steps of AP at NMJ?

Answer 1

1. AP arrives at the terminal button and the voltage-gated Ca channels open
2. The release of Ca leads to the release of ACh into the synapse
3. ACh will diffuse across synapse and bind to Nm receptors on motor end plate
4. ACh will open channels for Na and K on MEP
5. net movement of + in cell (depolarization)
6. end plate potential (EEP) causes AP in muscle cell and causes contraction.

Question 2

Tensilon test

Answer 2

The administration of edrophonium to a patient that is expected to have MG

the acetylcholinesterase inhibitor (edrophonium) will improve symptoms in those with MG

MG is caused by circulating AB that damage nicotinic acetylcholine receptors

Question 3

Lambert-Eaton Myasthenic Syndrome (LEMS)

Answer 3

LEMS is caused by the autoimmune attack against Ca channels in the nerve endings at the NMJ

low Ca = low ACh

different than MG because LEMS improves with physical activity

Question 4

Botulinum toxin / Botulism / botox

Answer 4

protease that prevents the release of ACh vesicles from the NMJ

Question 5

Tubocurarine and curareis

Answer 5

tubocurarine = Nm receptor antagonist and used to relax skeletal muscles

curareis = competitive inhibitor of skeletal muscle (will not allow muscle contraction)

Question 6

Resting muscle vs contracting muscle

Answer 6

resting:
low Ca concentration intercellularly
Ca in SR
Ca bound to calsequestrin in SR

contracting:
SR is only source for Ca during contraction
high intercellular concentration of Ca

Question 7

Functions of titin and nebulin

Answer 7

titin: provides elasticity and stabilizes myosin
nebulin: aligns actin

Question 8

How does calcium exit SR and enter cytoplasm?

Answer 8

AP in the t-tubule alters conformation of the DHP receptor

The DHP receptor opens the RyR channel, which releases calcium

Ca will then bind to troponin (allowing actin and myosin binding)

Question 9

Malignant hyperthermia

Answer 9

dysregulation of calcium release (RyR receptors)

certain anesthetic agents, strenuous exercise, or high environmental heat can trigger this abnormal release of Ca from the SR

results in sustained muscle contraction and heat production

treatment: Dantrolene (binds to RyR)

Question 10

Excitation-Contraction Coupling

Answer 10

1. increase in intracellular calcium
2. calcium binds to troponin
3. troponin will pull tropomyosin away from actin
4. myosin binds to actin and completes power stroke
5. actin filament moves

Question 11

Crossbridge cycle

Answer 11

1. ATP binds to myosin (myosin releases actin)
2. myosin will hydrolyze the ATP
3. power stroke begins when tropomyosin moves away from actin
4. myosin ends ADP after power stroke

Question 12

sarcomere contraction

Answer 12

H and I band both shorten

A band does not change

Question 13

Isometric vs isotonic contraction

Answer 13

isometric: 
length is consistent
load is greater than tension 
the muscle does not shorten, load is not lifted 
elastic elements stretch 

isotonic: 
constant tension
tension is greater than the load 
load is lifted and the muscle shortens  
elastic elements are already stretched

Question 14

four phases of isotonic contraction

Answer 14

phase 1: isometric contraction (length is not changing)

phase 2: isotonic contraction (length is changing)

phase 3: isotonic relaxation

phase 4: isometric relaxation (resting)

Question 15

isometric graph vs isotonic graph

Answer 15

isometric = bell-shaped curve (force/time)
the muscle does not shorten

isotonic = flat-topped curve (force/time)

Question 16

How to increase pre-load?

Answer 16

increase Fmax (shifts curve to right)

increase velocity

no change in Vmax (cant be changed)
(determined by myosin ATPase activity)

Question 17

Red (type I, slow oxidative) vs White (type II, fast glycolytic) muscle types

Answer 17

Red: 
long-term effect
lower myosin ATPase activity 
large amounts of myoglobin 
high capacity for aerobic metabolism 
slow twitch (fatigue-resistant) 

White: 
used short-term 
high myosin ATPase activity
low myoglobin 
high capacity for anaerobic activity 
fast twitch

Question 18

Ways to regulate muscular force?

Answer 18

graded muscle contractions
tension produced by each fiber and number of fibers

1. temporal summation
2. spatial summation

Question 19

summation and tetanus

Answer 19

tetanus is a toxin that inhibits the release of GABA
this leads to the increased frequencies due to continuous stimulation.
release of calcium exceeds the re-uptake, eventually saturating the system.
muscles will thus not relax

treatment:
antitoxin
diazepam (GABA agonist) = control spasms