Neuromuscular Junction Flashcards

1
Q

what are the five steps of synaptic transmission
5 possible targets of drugs and toxins

A

synthesis of neurotransmitters
storage of neurotransmitters in vesicles
exocytosis of transmitters
transmitters bind to post-synaptic receptors
transmitters dissociate

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2
Q

why are neurotransmitters stored in vesicles in the pre-synaptic neuron

A

prevent them from metabolism
package them together

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3
Q

what causes exocytosis of transmitters from pre-synaptic neurons

A

opening of voltage-gated calcium channel

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4
Q

what do transmitters do when they bind post-synaptic receptors?

A

cause conformational changes
change the activity of the receptor

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5
Q

what facilitates transmitter dissociation
what happens to them afterwards

A

enzymes
broken down into components, some recycled

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6
Q

what is an agonist

A

substances which bind specific receptors and elicit a biological response

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7
Q

agonists:
affinity?
efficacy?
Reversible?

A

posses affinity and efficacy
always reversible

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8
Q

what is an antagonist

A

substances which bind specific receptors and do not activate them

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9
Q

antagonists:
affinity?
efficacy?
Reversible?

A

posses affinity but lack efficacy
not always reversible

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10
Q

which has higher binding affinity, antagonists or agonists?
how can the other still bind first

A

antagonists tend to have a higher affinity
agonists can bind first if at a higher concentration

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11
Q

what are the two moieties of acetylcholine

A

acetyl moiety
choline moiety

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12
Q

which subunit of nicotinic receptors does ACh bind
transmitter gated Na+ ion channels

A

alpha

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13
Q

how can a Na+ ion channel be isolated from a post-synaptic neuron

A

patch-clamp

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14
Q

how can mepps and epps be measured

A

microelectrodes

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15
Q

explain mepps

A

miniature end plate potentials
spontaneous depolarisations
depolarisation caused by a single vesicle
not sufficient to cause an AP

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16
Q

explain epps

A

end plate potentials
large depolarisation of the endplate of muscle cell
can initiate APs
summation of mepps in response to nerve impulse
muscle contraction

17
Q

how and why is the size of epps reduced for study

A

using a high Mg2+, low Ca+ buffer (Mg blocks Ca2+ channels, calcium triggers exocytosis)
prevent the glass microelectrode from breaking

18
Q

what does quantal mean in relation to transmitter release?

A

the amplitude of the epp is a multiple of the amplitude of the mepp
smallest epp = mepp

19
Q

what is quantal content
how is it calculated

A

number of vesicles per stimulation
QC=mean EPP amplitude / mean MEPP amplitude (mV)

20
Q

what enzyme synthesises ACh and from what

A

Choline acetyltransferase (CAT)
from choline and acetyl-CoA

21
Q

explain the reuptake of choline

A

Na+ dependant
blocked by hemichlonium 3

22
Q

effect on mepp, epp and QC if transmitter synthesis is blocked

A

less Ach per vesicle
-mepp and epps decreased equally
-no change in QC

23
Q

explain storage of ACh

A

transported into vesicles
blocked by inhibition of transporter

24
Q

effect on mepp, epp and QC if ACh storage is blocked

A

less Ach per vesicle
-mepp and epps decreased equally
-no change in QC

25
Q

explain the process of vesicle exocytosis

A

AP causes the opening of Na+ channels
depolarisation causes the opening of Ca2+ channels
Calcium enters the cell and causes vesicles to move towards the synapse and fuse with the membrane
depolarisation also causes the opening of K+ channels
K+ exits the cell leading to repolarisation

26
Q

target and effect of tetrodotoxin

A

blocks Na+ channels
no action potential - no release - no epp
no effect on mepps

27
Q

target and effect of conotoxins

A

blocks Ca2+ channels
less influx - less release - decreased epp
no effect on mepp - lower QC

28
Q

target and effect of dendrotoxin

A

blocks K+ channels
prolonged APs - greater release - increased epp
no effect on mepp - QC increased

29
Q

target and effect of botulinum toxin

A

blocks vesicular fusion with the membrane
decreased release - decreased epp
no effect on mepp - QC decreased

30
Q

target and effect of tubocurarine
how can it be reversed

A

blocks nicotinic ACh receptors (antagonist)
prevents sufficient Na+ influx for an AP paralyses skeletal muscle - decrease mepp and epp
treated with neostigmine

31
Q

target and effect of alpha-bungarotoxin
how can it be reversed

A

blocks nicotinic ACh receptors (antagonist)
prevents sufficient Na+ influx for an AP paralyses skeletal muscle - decrease mepp and epp
irreversible

32
Q

target and effect of succinylcholine

A

agonist of nicotinic ACh receptors
leads to paralysis by rapidly and repeatedly binding and leading to desensitization

33
Q

what is the effect of anticholinesterases

A

increase the effects of ACh
prolonged APs

34
Q

what are anticholinesterases used for

A

reverse muscle relaxants
treat myasthenia gravis and Alzheimer’s

35
Q

target and effect of organophosphates

A

bind acetylcholine esterase and prevent its action
recovery requires the synthesis of new enzymes (weeks)

36
Q
A
37
Q
A