Lecture 10 - Skeletal Muscle Neurophysiology 2

Question 1

what are the 9 steps that occur in the sequence of events that occur at the NMJ?

Answer 1

1) AP initiates in an axon
2) voltage gated Ca2+ channels open causing an Ca2+ influx
3) Ca2+ triggers vesicle fusion, releasing Ach that diffuses into the cleft
4) Ach binds to nAchR’s on the muscle fibre
5) nAchR channels open and Na+ enters
6) local depolarisation spreads to the extra junctional membrane
7) depolarisation opens voltage gated Na+ channels triggering a muscle AP
8) AP propagates along the muscle fibre
9) Ach is degraded by AchE

Question 2

what composes the nicotinic acetylcholine receptor (nAchR) in terms of subunits and transmembrane domains?

Answer 2

composed of 5 subunits with 4 transmembrane domains

Question 3

what do the subunits surround in nAchR’s?

Answer 3

subunits surround pores in the membrane

Question 4

what is the pore of nAchR’s?

Answer 4

the pore is gated and normally closed

Question 5

when do the chemically gated nAChR channels open?

Answer 5

open when 2 Ach molecules bind and this causes depolarisation due to Na+ entry

Question 6

how is depolarisation of the nAChR’s degraded?

Answer 6

degraded by AchE in folds

Question 7

what are non-selective cation channels permeable to?

Answer 7

permeable to both Na+ and K+

Question 8

where are the 2 Ach molecules released from?

Answer 8

released from presynaptic vesicles

Question 9

where are muscarinic acetylcholine receptors present?

Answer 9

present in the CNS, ANS and smooth muscle

Question 10

how does the muscarinic acetylcholine receptors function?

Answer 10

functions through indirect gating via a G protein

Question 11

what do muscarinic acetylcholine receptors signal via?

Answer 11

signal via a GPCR to change cell signalling

Question 12

what do muscarinic acetylcholine receptors indirectly regulate?

Answer 12

indirectly regulate the opening of ion channels (not found in skeletal muscle)

Question 13

what are metabotropic receptors in a complex with?

Answer 13

in a complex with G proteins

Question 14

what occurs when Ach binds to muscarinic acetylcholine receptors?

Answer 14

this causes a conformational change which affects the the affinity of the G alpha subunit of the G protein complex where GDP is exchanged for GTP. In the GTP bound form the G alpha subunit can dissociate the other G proteins and regulate other processes in the cell and directly interact with ion channels

Question 15

what is myasthenia gravis?

Answer 15

an autoimmune disorder of the NMJ where antibodies to muscarinic nAchR’s are produced and this reduces the number of receptors and blocks receptors. This results in an inflammatory response that damages the NMJ (motor endplate).

Question 16

what occurs if the NMJ (motor endplate) is damaged?

Answer 16

damage results in reduced NMJ function causing muscle weakness, particularly of frequently used muscles

Question 17

what are myasthenia gravis symptoms induced by?

Answer 17

induced by sustained muscle contraction

Question 18

what occurs in a normal NMJ in terms of AP’s and the reusable pool of Ach?

Answer 18

in a normal NMJ a rapid sequence of many AP’s in the nerve results in a slight depletion of the reusable pool of Ach and this results in less Ach released per AP. However, the amount released is normally still enough Ach by a single AP to initiate an AP in muscle
- has a high safety factor

Question 19

what occurs in a damaged NMJ in terms of AP’s and the reusable pool of Ach?

Answer 19

when the number of receptors is reduced as in myasthenia gravis, the normal drop in Ach for later impulses may cause failure of transmission as safety factors are reduced and depolarisation gets smaller

Question 20

how is myasthenia gravis treated?

Answer 20

can be treated by drugs that block AchE to help keep Ach around to have a larger sustained depolarisation by delaying the breakdown of Ach to build up Ach levels