Action potentials: generation and propagation

Question 1

What is the structure of a voltage-gated calcium channel in relation to its pore-forming α1 subunit?

Answer 1

CaV’s α1 has 4 domains (I - IV) each containing 6 transmembrane helices (S1–S6).

Question 2

What is the structure of a voltage-gated potassium channel in relation to its pore-forming α subunit?

Answer 2

Kv has 4 identical SUBUNITS (not domains; smaller) which each contain 6 transmembrane helices. The subunits are arranged as a ring to each form a wall for the transmembrane pore.

Question 3

What is the structure of a voltage-gated sodium channel in relation to its pore-forming α1 subunit?

Answer 3

NaV’s α pore has 4 domains (I - IV) each containing 6 transmembrane helices (S1–S6).

Question 4

How are voltage-gated channels activated?

Answer 4

Each set of 6 transmembrane helices has a voltage sensor (e.g. S4 in sodium channels)

Question 5

What can cause summation to reach threshold potential to initiate an AP? Give examples.

Answer 5

Small capacitance ligand-gated cation(+) channels e.g.:

• Nicotinic ACh receptors at neuromuscular junctions
• 5HT3 receptors at CNS synapses/smooth muscle
• P2X receptors at CNS synapses/smooth myscle

Question 6

What happens when the threshold potential is reached?

Answer 6

If summation of graded potentials (from ligand-gated cation channels etc) reaches the threshold, the voltage-gated Na+ channel opens and an AP (action potential) is generated.

Question 7

Why are APs short lived?

Answer 7

Voltage-gated K+ channels (responding to the AP’s depolarisation) soon open to reverse the change in Vm.

Question 8

What is the action of Ouabain as a Na+/K+-ATPase inhibitor?

Answer 8

Reduces the size of APs progressively until the membrane Na+ gradient is reduced to the point where APs can be initiated, but fail/don’t follow through.

Question 9

What is the action of Tetrodotoxin (TTX) as a neuronal VGSC (voltage-gated sodium channel) inhibitor?

Clue: Puffer fish.

Answer 9

Abolishes AP (but not graded postsynaptic potential).

• Selective for skeletal muscle, the puffer fish’s venom leaves the victim paralysed.

Question 10

How do action potentials encode their information/differentiate between different ones?

Answer 10

APs encode information by frequency, not amplitude.

Question 11

What is the limiting factor regarding the speed of APs to encode information?

Answer 11

APs can only be sent so often; upper frequency limit imposed by refractory period (cell has to recover before next AP).

Question 12

What are the 3 states of a voltage-gated channel and the activity of m & h gates associated?

Answer 12

Resting; m gate (activation) is closed, h gate (inactivation) is open
Activated; threshold potential reached; m gate open (value approaching 1), h gate open (flow of Na+ with both gates open)
Inactivated; m gate open (pore is open) but h gate closed (value is 0; refractory period)

Question 13

Describe the propagation of an AP along an axon

Answer 13

Local currents; depolarisation from an AP set up local currents in both directions (but AP cannot go backwards as Na+ channels are refractory), thus AP moves forwards.

Question 14

What factors determine the speed of conduction?

Answer 14

• Temperature
• Axon diameter (greater cytosol = lower longitudinal resistance thus faster conductance; membranes have high charge storage (capacitance)
• Myelination

Question 15

How does myelination differ from the CNS to the PNS?

Answer 15

CNS: oligodendrocytes provide myelination, extending its processes to up to 50 axons forming myelin sheaths.
PNS: (multiple) schwann cells wrap an axon with myelin

Question 16

How do myelinated APs propagate?

Answer 16

Saltatory conduction; APs ‘jump’ from Nodes of Ranvier (io channels only available at nodes)