Chp. 26: Neuromuscular Blockade

Question 1

Where do NMBAs exert their action?

Answer 1

NMJ

Question 2

Describe the activity of the NMJ

Answer 2

Presynaptic cell synthesizes and stores ACh is vesicles (reserve AND readily available populations) –> Depolarization results in Ca2+ influx via voltage-gated channels –> Mobilization of vesicles is triggered and ACh is released into the cleft –> Two ACh molecules interact with both alpha subunits of nAChR on post-synaptic cell–> Conformational change –> Na+ influx into skeletal muscle –> Depolarization of post-synaptic cell activates voltage-gated Na+ channels –> AP is propagated –> Muscle contracts

Question 3

What is the duration of interaction between ACh and nAChR?

Answer 3

Very brief

Question 4

What terminates the effects of ACh?

Answer 4

Prompt hydrolysis by acetylcholinesterase enzyme into choline and acetic acid. Reduction in [ACh] in cleft favors movement away from nAChR

Question 5

What is the effect of absence of Ca2+ on ACh release? Of doubling the calcium?

Answer 5

Absence: Absence of ACh release and muscular contractions

Doubling: 16-fold increase in amount of released ACh

Question 6

What accounts for the reserve of the NMJ?

Answer 6

Only a fraction of available ACh vesicles are released under normal circumstances and only a small number of available nAChR need to be activated for maximal muscle cell depolarization

Question 7

What are the binding sites of ACh and NMBAs?

Answer 7

Two alpha1 subunits on postsynaptic receptor

Question 8

How do fetal and mature forms of the nAChR differ?

Answer 8

Gamma subunit in fetal subtype, epsilon subunit in mature form

Question 9

What nAChR subtypes are found during development?

Answer 9

alpha7 and fetal subtype

Question 10

When do fetal and alpha7 subtypes of nAChR proliferate?

Answer 10

During abnormal conditions resulting in decreased muscle activity (poor innervation, prolonged immobilization, increased muscle catabolism)