Neuromuscular junction Flashcards

1
Q

How is signal passed between nerve and muscle?

A

At neuromuscular junction onto motor end plate

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2
Q

What is cellular response of depolarisation at end of synaptic bouton?

A

Depolarisation (influx of Na+) causes Ca2+ V gated channels to open
Ca+ enters synaptic bouton

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3
Q

What does increase in Ca2+ mean in synaptic bouton?

A

Neurotransmitter is released via exocytosis

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4
Q

Levels of Ca2+ normally inside

A

Normally very low in cells

Ca2+ influx can raise internal concentration significantly

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5
Q

what does increasing frequency of action potentials do?

A

Increases the amount of Ca2+ entry and increases transmitter released

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6
Q

structure of V gated Ca2+ channels

A

similar to na+
1 a subunit: 4 sections
membrane spanning

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7
Q

What blockers block L type Ca2+ channels?

A

DHP (dihydropyridines)

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8
Q

what is DHP used for?

A

Regulating BP

Blocks L type Ca2+ cells present in smooth muscle cells of vessels (less contraction = lower BP)

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9
Q

Subunits associated with Ca2+ and Na+ channels

A

phosphorylation sites

increase ability to open (more likely to contract)

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10
Q

what does Acetylcholine esterase do?

A

breaks down Ach - not high concentrations in synaptic cleft

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11
Q

how does Ca2+ enter cell?

A

through V gated Ca2+ channels

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12
Q

what does Ca2+ bind to when in cell?

A

Synaptotagmin

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13
Q

What does Ca2+ binding with synaptotagmin cause?

A

Vesicles bought close to membrane

Interact with snare complex

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14
Q

What does snare complex do?

A

Makes fusion pore

Ach exits via this pore

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15
Q

nAchR (nicocinic Ach receptor) type

A

ligand gated

permeable to cations

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16
Q

What does nAchR permeability mean?

A

allows Na+ into cell and K+ out of cell

Driving force of Na+ is higher due to membrane potential being nearer Ek

17
Q

What occurs when Na+ moves into cell via nAchR?

A

Membrane reaches threshold and depolarises end plate

18
Q

What is transmitter release dependent on?

A

Ca2+ entry to cell

If you lower external Ca2+ conc, end plate potentials decrease in amplitude

19
Q

How does end plate potential activate muscle action potential?

A

brief depolarisation activates adjacent Na+ channels (charge spreads)
propagates along muscle fibre

20
Q

How does curare cause paralysis?

A

Blocking transmission between nerve and muscle

used in hunting

21
Q

2 types of nicotinic blockers

A

competitive blocker

Depolarizing blocker

22
Q

Competetive blocker example

A

D-tubocurarine (d-TC)

23
Q

how does d-TC work?

A

Competitively binds to nAchR (receptor site) and prevents Ach from binding

24
Q

can d-TC effects be overcome?

A

Yes, increasing Ach concentration

25
Q

How do depolarising blocks work?

A

Maintain depolarisation
Fail to activate adjacent Na+ channels as they are inactivated
May get initial quivering but then nothing

26
Q

Depolarising blocker example

A

Succinylcholine

27
Q

When are neuromuscular blockers used?

A

Surgery - but can look like under general anaesthetic but can still feel pain just cannot move (paralysed)

28
Q

Myasthenia Gravis

A

Autoimmune disease targeting nAch receptors
Antibodies attack receptor - loss of function and degradation
End plate potentials cannot reach threshold

29
Q

Myasthenia Gravis signs/symptoms

A

weakness
increases with exercise
fatigue
end plate potentials reduced in amplitude = muscle weakness/fatigue

30
Q

Diagnosis myasthenia gravis

A

Facial weakness provoked by repeated facial movements
Edrophonium chloride injection (anticholinesterase)
Facial weakness relieved rapidly = positive for myasthenia gravis

31
Q

Organophosphate poisoning sources

A

Insecticides
Pentavalent phosphorous compounds
Nerve agents (sarin, Novichok)

32
Q

Organophosphate poisoning mechanism

A

Acetylcholinesterase inhibitors form a stable irriversible covalent bond to the enzyme
Ach not broken down

33
Q

organophosphate symptoms

A
SLUDGE
salivation
lacrimation 
urination
defecation 
gi cramps
emesis
34
Q

Recovery organophosphate poisoning

A

Synthesis of new actylcholinesterase needed

takes weeks

35
Q

Other mechanisms of Ach

A

Binds to muscarinic ach receptors on target tissues of autonomic nervous system

36
Q

nAchR vs mAchR

A

nAchR - fast depolarisation as its ligand gated

mAchR - slower response, G coupled proteins which trigger cascade of events in cell