Neuromuscular junction

Question 1

How is signal passed between nerve and muscle?

Answer 1

At neuromuscular junction onto motor end plate

Question 2

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

Answer 2

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

Question 3

What does increase in Ca2+ mean in synaptic bouton?

Answer 3

Neurotransmitter is released via exocytosis

Question 4

Levels of Ca2+ normally inside

Answer 4

Normally very low in cells

Ca2+ influx can raise internal concentration significantly

Question 5

what does increasing frequency of action potentials do?

Answer 5

Increases the amount of Ca2+ entry and increases transmitter released

Question 6

structure of V gated Ca2+ channels

Answer 6

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

Question 7

What blockers block L type Ca2+ channels?

Answer 7

DHP (dihydropyridines)

Question 8

what is DHP used for?

Answer 8

Regulating BP

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

Question 9

Subunits associated with Ca2+ and Na+ channels

Answer 9

phosphorylation sites

increase ability to open (more likely to contract)

Question 10

what does Acetylcholine esterase do?

Answer 10

breaks down Ach - not high concentrations in synaptic cleft

Question 11

how does Ca2+ enter cell?

Answer 11

through V gated Ca2+ channels

Question 12

what does Ca2+ bind to when in cell?

Answer 12

Synaptotagmin

Question 13

What does Ca2+ binding with synaptotagmin cause?

Answer 13

Vesicles bought close to membrane

Interact with snare complex

Question 14

What does snare complex do?

Answer 14

Makes fusion pore

Ach exits via this pore

Question 15

nAchR (nicocinic Ach receptor) type

Answer 15

ligand gated

permeable to cations

Question 16

What does nAchR permeability mean?

Answer 16

allows Na+ into cell and K+ out of cell

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

Question 17

What occurs when Na+ moves into cell via nAchR?

Answer 17

Membrane reaches threshold and depolarises end plate

Question 18

What is transmitter release dependent on?

Answer 18

Ca2+ entry to cell

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

Question 19

How does end plate potential activate muscle action potential?

Answer 19

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

Question 20

How does curare cause paralysis?

Answer 20

Blocking transmission between nerve and muscle

used in hunting

Question 21

2 types of nicotinic blockers

Answer 21

competitive blocker

Depolarizing blocker

Question 22

Competetive blocker example

Answer 22

D-tubocurarine (d-TC)

Question 23

how does d-TC work?

Answer 23

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

Question 24

can d-TC effects be overcome?

Answer 24

Yes, increasing Ach concentration

Question 25

How do depolarising blocks work?

Answer 25

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

Question 26

Depolarising blocker example

Answer 26

Succinylcholine

Question 27

When are neuromuscular blockers used?

Answer 27

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

Question 28

Myasthenia Gravis

Answer 28

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

Question 29

Myasthenia Gravis signs/symptoms

Answer 29

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

Question 30

Diagnosis myasthenia gravis

Answer 30

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

Question 31

Organophosphate poisoning sources

Answer 31

Insecticides Pentavalent phosphorous compounds Nerve agents (sarin, Novichok)

Question 32

Organophosphate poisoning mechanism

Answer 32

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

Question 33

organophosphate symptoms

Answer 33

``` SLUDGE salivation lacrimation urination defecation gi cramps emesis ```

Question 34

Recovery organophosphate poisoning

Answer 34

Synthesis of new actylcholinesterase needed | takes weeks

Question 35

Other mechanisms of Ach

Answer 35

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

Question 36

nAchR vs mAchR

Answer 36

nAchR - fast depolarisation as its ligand gated mAchR - slower response, G coupled proteins which trigger cascade of events in cell