week 12 L2: Skeletal neuromuscular junction Flashcards

1
Q

What is MEPPS?

A

Miniature end plate potentials
Can summate to cause a EPP caused by the random release of single quanta of neurotransmitter from a resting presynaptic terminal

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2
Q

what causes MEPPS ?

A

ACh released from a single vesicle activates many receptors

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3
Q

What does ACh binding to the nicotinic cation channel do?

A

channel opens and Na+ flux into cell

local depolarisation at endplate

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4
Q

What is electron microscopy?

A

reveals vesicle in the apparent act of exocytosis

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5
Q

What does black widow spiders venom influence?

A

spontaneous transmitter release

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6
Q

What does an increase in MEPPS cause?

A

muscle spasm, massive ACh release

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7
Q

How can the muscle spasm be reversed?

A

depletion of vesicles
inhibition on endocytosis (dont endocytose vesicle)
distend terminal
paralysis

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8
Q

What is EPP?

A

large depolarisation of endplate region of muscle cell
endplate potential
voltages which cause depolarisation

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9
Q

What does a large EPP cause?

A

a large enough depolarisation activates postsynaptic Na+ channels= AP

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10
Q

What factors contribute to a muscle fibre action potential?

A

EPP needed above threshold then with the help of Na+, depolarisation in the endplate region can cause a muscle fibre action potential.

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11
Q

What mV does the cell need to depolarise to for Na+ to open? EP

A

-40mV

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12
Q

What problem is there with the cell attached path technique?

A

muscle fibre contraction breaks glass microelectrode

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13
Q

What needs to be reduced so cell attached technique can be used on muscle fibre?

A

need to reduce EPP to study neurally evoked transmitter release.

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14
Q

How to reduce a muscle contraction so it can be analysed?

A

use a buffered solution of high ratio of Mg:Ca

magnesium blacks the Ca2+ channels, so just mepp occurs not a high enough EPP for a contraction

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15
Q

What is the relationship between amplitudes epp and mepp?

A

the amplitude of epp is a multiple of the amplitude mepp (smallest amplitude)
QUANTAL

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16
Q

What is quantal content (Q.C)?

A

number of vesicles/stimuli

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17
Q

Quantal Content equation?

A

(mean EPP amplitude mv) / (mean MEPP amplitude mV)

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18
Q

What does the mean epp amplitude correspond to in the Q.C equation?

A

in response to motor nerve stimulation

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19
Q

What does the mepp amplitude correspond to in the Q.c equation?

A

occur spontaneously (without nerve stimulation)

20
Q

What does quanta mean in the context of NMJ?

A

release of a vesicle gives a quanta

21
Q

What does a change in epp and no change in mepp mean?

A

toxin works pre-synamptiaclly

act pre-synamptically to increase neurally evoked transmitter release

22
Q

What enzyme is used to covert choline to ACh?

A

CAT

Choline acetyl transferase

23
Q

Where does the Acetyl-Co-A come from?

A

Mitochondria

24
Q

Where is the choline come from?

A

from re-uptake from NMJ

25
Q

What are the precursors for Acetyl choline production?

A

Acetyl-Co-A and choline

26
Q

How is Acetyl choline made at the terminal of the presynaptic neurone?

A

Enzyme CAT coverts acetyl-Co-A to Co-A, adding the acetyl to the choline and synthesise together to make ACh

27
Q

what is a choline receptor called?

A

Choline transporter

28
Q

What is choline re-uptake dependent on?

A

Na+ dependent. If Na+is at high concentration in terminal then an AP is occurring so more ACh is needed.
voltage dependent, Na+ creates a depolarisation in terminal

29
Q

what blocks a Choline transporter?

A

Hemicholinium 3

30
Q

What is the impact of Hemicholinium 3?

A

Less ACh
Amplitude of epp and mepp decreased
No change in quantal content

31
Q

What drug effects storage?

A

Vesamicol

32
Q

How does Vesamicol effect storage?

A

inhibits ACh vesicular transporter
blocks transport of ACh into vesicle
Less ACh into vesicle
Decrease in epp and mepp, no change Q.C

33
Q

How does Tetrodotoxin effect the body?

A

causing paralysis of diaphragm=respiratory failure

similar

34
Q

What is the source of Tetrodotoxin?

A

powerful toxin produced by bacteria and concentrated in pufferfish e.g liver

35
Q

What 4 drugs effect release?

A

tetrodotoxin, conotoxin, dentrotoxin, Botulinum toxin

36
Q

How does tetrodotoxin effect release?

A

blocks Na+ channels (no Na into terminal)

No AP, no release, no EP

37
Q

How does conotoxins effect release?

A

Block voltage gated Ca2+ channels

Decrease Ca2+ influx, decrease release

38
Q

Conotoxin effect on amplitude?

A

epp decrease
mepp no change
decrease Q.C

39
Q

Does conotoxin work pre or post synaptically?

A

pre-synaptically

40
Q

how does dentrotoxin effect release?

A

blocks voltage gated K+ channels

prolonged AP, Ca2+ influx, increased release

41
Q

Dentrotoxin effect on amplitude?

A

epp increased
no change in mepp
increased QC

42
Q

What bacterium is Botulinum toxin from?

A

bacterium clostridium botulinum

43
Q

What can botulinum toxin lead to?

A

respiratory paralysis

44
Q

What muscle disorders can Botulinum clinically treat?

A

chronic migraine, excessive underarm sweating, neuropathic pain

45
Q

What is Botulinum also known as?

A

Botox

46
Q

How does Botulinum effect release?

A

Blocks vesicle fusion by cleaving a vesicular protein required for exocytosis, decrease release

47
Q

Botulinum effect on amplitude?

A

epp decrease
mepp no change
decrease QC