Synapse/NMJ

Question 1

What is a neuromuscular junction (NMJ)?

Answer 1

Specialised synapse between nerve and skeletal muscle fibres

Question 2

What happens when an AP arrives at a nerve terminal?

Answer 2

Causes depolarisation which causes VG Ca2+ channels to open, Ca2+ enters the nerve cells causes vesicles containing neurotransmitter to fuse with the presynaptic membrane and release of neurotransmitters into the synaptic cleft.

Question 3

What is the effect of a strong signal on neurotransmitter release?

Answer 3

Strong signal = high frequency = lots of Ca2+ enters nerve cell = lots of neurotransmitters released

Question 4

What is the structure of VG Ca2+ channels?

Answer 4

Similar structure to VG Na channels
(Single peptide subunit (containing 4 repeating domains)
Each domain has 6 TMS alpha helices
Between TMS helices 5 and 6 there is a pore region
TMS region 4 is positively charge
Between TMS helices 3 and 4 there is an inactivation particle)

Question 5

Where are L type VG Ca channels found primarily?

Answer 5

Muscle
Neurones
Lungs

Question 6

What are L type VG Ca channels blocked by?

Answer 6

dihydropyridines e.g. Nifedipine

Main target for drugs

Question 7

What is the effect of phosphorylation by protein kinase A on VG Ca channels?

Answer 7

Increases Ca channel activity

Question 8

What causes VG Ca channel inactivation?

Answer 8

CA dependent - increased intracellular Ca leads to Ca channel j activation

Question 9

What does calcium bind to on vesicles containing neurotransmitter? And how does this cause it’s release?

Answer 9

Synaptotagmin - brings vesicles confining neurotransmitter close to membrane, interacts with snare complex causing a fusion pore, where neurotransmitter can enter synaptic gap

Question 10

What happens when Ach binds nicotinic Ach receptors?

Answer 10

When 2 Ach bind receptor causes a conformational change, opening the pore, allowing entry of cations (non selective - K and Na). Result is depolarisation, over threshold, AP passed on.

Question 11

How is Ach removed from the synaptic cleft after action?

Answer 11

Quickly broken down by Ach esterase on post synaptic membrane

Question 12

What is the reversal potential?

Answer 12

Where there is no net charge flow for a particular ion across the membrane

Question 13

How does depolarisation from Ach receptors causes muscle AP at NMJ?

Answer 13

Adjacent to the NMJ are VG Na channels, which are activated by the depolarisation from Ach receptors (due to spread of local charge) causes propagation of the AP which leads to muscle contraction

(Excitation contraction coupling)

Question 14

Succinylcholine is a depolarising blocked of Ach receptors, how does it work?

Answer 14

Binds to Ach receptors causing them to remain open, therefore post synaptic membrane remains depolarised. Causes the inactivation of VG Na channels which cannot be activated until hyperpolarisation therefore AP cannot be passed on

Question 15

Tubocurarine (d-TC) is a competitive blocker of Ach receptors. How does it work?
How can it be overcome?

Answer 15

Competitively binds receptor - channel closed, post synaptic membrane not depolarised.

When Ach concentration increased, increased likelihood of Ach binding before blocker - may overcome blocking.

Question 16

What is myasthenia gravis ?

Answer 16

An auto immune disease targeting Ach receptors, where antibodies are directed against nAchR on the post synaptic membrane of skeletal muscle. Lead to loss of functional nAchR by complement mediated lysis and receptor degradation. Causes endplate potential to decrease in amplitude - leading to weakness and fatigue (can’t reach threshold)

Question 17

Where are muscarinic Ach receptor located?

Answer 17

Between postganglionic neurones and target tissue (on parasympathetic branch of autonomic nervous system)