8. Electrical Excitability

Question 1

What are the key ion channels in nerve terminals?

Answer 1

Voltage gated Na+, K+ and Ca2+ channels.

Question 2

What happens at the nerve terminal from depolarisation?

Answer 2

Voltage-gated Ca2+ channels open and Ca2+ enters so [Ca2+]i increases and there is release of neurotransmitter.

Question 3

What is the structure of voltage-gated Ca2+ channels?

Answer 3

Similar to VGNa+ channels - four parts in one protein chain, with a pore forming region that differs from Na+ (to only allow Ca2+ entry through it).

Question 4

What are the subunits in Na+ channels?

Answer 4

B1, B2, a (pore forming subunit).

Question 5

What are the subunits in Ca2+ channels?

Answer 5

Y, B, a1 (pore forming subunit), a2 and o.

Question 6

Where do nerve and skeletal muscle fibres synapse?

Answer 6

At the neuromuscular junction.

Question 7

What breaks down ACh at the neuromuscular junction?

Answer 7

Acetylcholine esterase.

Question 8

What are some of the features of a neuromuscular junction?

Answer 8

Post junction folds, synaptic cleft, acetylcholine receptors.

Question 9

How are transmitters released?

Answer 9

Ca2+ enters through Ca2+ channels and binds to synaptotagmin. The vesicle is brought close to the membrane and the snare complex makes a fusion pore. Transmitter is released through this pore.

Question 10

What is the effect of ACh binding to nicotinic receptors?

Answer 10

Conformational change of the receptor so the pore opens.

Question 11

In the Amazon, the poison curare is used to paralyse monkeys for food. How does curare work?

Answer 11

By blocking the transmission between nerve and muscle.

Question 12

What are two examples of nicotinic ACh receptor blockers that act via different mechanisms?

Answer 12

Tubocurarine - competitive blocker.

Succinylcholine - depolarising blocker (used more in medicine).

Question 13

How does d-tubocurarine work?

Answer 13

By competitively blocking nicotinic receptors. It has a similar shape to ACh but the channel remains closed after binding and this stops ACh binding and opening the channel. Lots of ACh can overcome some of the effects of the block.

Question 14

How does succinylcholine work?

Answer 14

By blocking depolarisation. Succinylcholine binds to ACh nicotinic receptors and causes them to fire an action potential so the area of membrane next to it has become accommodated as Na+ channels become inactivated.

Question 15

What are miniature end-plate potentials caused by?

Answer 15

Spontaneous release of vesicles at a very low level. This leads to a vesicle binding to the membrane and releasing ACh.

Question 16

What is Myasthenia gravis?

Answer 16

An autoimmune disease targeting nACh receptors.

Question 17

What are the symptoms of Myasthenia gravis?

Answer 17

Profound weakness, increasing weakness with exercise.

Question 18

What causes the symptoms of Myasthenia gravis?

Answer 18

Antibodies directed against nAChR on the post synaptic membranes of skeletal muscle. This leads to a loss of functional nAChR by complement mediated lysis and receptor degradation. End plate potentials are reduced in amplitude so cause muscle weakness and fatigue.

Question 19

How are miniature endplate potentials affected in Myasthenia gravis?

Answer 19

The endplate potentials are much smaller. Each ACh release produces a smaller response than normal due to fewer nAChR available.

Question 20

Summarise the transmission at the NMJ.

Answer 20

Action potential arrives at NMJ. And opens VG Ca2+ channels. Ca2+ enters and initiates exocytosis of ACh containing vesicles. ACh binds to nicotinic ACh receptors on the end-plates, so they open and cations flow causing depolarisation. The adjacent muscle membrane is depolarised and activates VG Na+ channels - initiating an action potential and causing contraction of the muscle fibre.

Question 21

How do nicotinic and muscarinic ACh receptors act differently?

Answer 21

NAChR has fast depolarisation because it is a ligand gated ion channel.
mAChR has slower depolarisation I because they are coupled to G-proteins which trigger a cascade of events in the cell.