Action Potentials

Question 1

What is an AP?

Answer 1

Change in voltage across a membrane.

Question 2

How long do APs last? Why are they longer in cardiac cells?

Answer 2

• 0.5 ms in axons/skeletal muscles.

- 100 ms in SA node/cardiac ventricle. Longer duration allows CICR.

Question 3

What are APs generated by?

Answer 3

Increase in permeability to Na+, bringing membrane close to Na+ equilibrium potential.

Question 4

What is membrane conductance?

Answer 4

Permeability of a membrane to an ion. Dependent on:

1. Number of open channels for that ion.
2. Driving force (difference between membrane potential and equilibrium potential for the ion).

Question 5

How are the effects of MP changes on sodium and potassium currents measured?

Answer 5

Voltage-clamp technique

Question 6

Describe the opening and closing of ion channels during an AP.

Answer 6

1. Depolarisation
   - voltage-gated Na+ channels open - Na+ influx.
   - membrane depolarises - threshold is reached - positive feedback: more Na+ channels open.
2. Repolarisation
   - Na+ channels inactivate - Na+ influx stops.
   - voltage-gated K+ channels open - K+ efflux.
   - membrane repolarises (and even hyperpolarises as K+ channels stay open longer than necessary).

Question 7

What are the absolute and relative refractory periods?

Answer 7

• ARP = nearly all Na+ channels are inactivated - no AP can occur.
• RRP = Na+ channels are recovering from inactivation, excitability returns towards normal. AP can be initiated upon strong stimulation.

Question 8

Describe the structure of a voltage-gated sodium channel.

Answer 8

• 1 peptide consisting of 4 homologous repeats.
• Each repeat consists of 6 transmembrane spanning domains (helices) with a pore region between the 5th and 6th helices.
• 4th helice contains many positively charged aa - acts as voltage sensor.
• Inactivation particle located between 3rd and 4th repeats.

Question 9

How are sodium channels inactivated?

Answer 9

Inactivation loop can enter pore and block sodium flow. Membrane hyperpolarisation required to unblock pore.

Question 10

Describe the structure of voltage-gated potassium channels.

Answer 10

• Similar organisation to Na+ channels but consists of 4 alpha subunits of 1 repeat each.
• No inactivation particle.

Question 11

How do local anaesthetics such as procain act?

Answer 11

• Bind to and block Na+ channels - stops AP generation.
• 2 pathways:

1. Hydrophilic pathway
   - For anaesthetics that are weak bases - cross PM in un-ionised form.
   - Block channel more easily when it is open and have higher affinity for inactivated state - block in a use dependent manner.
2. Hydrophobic pathway
   - Lipid-soluble anaesthetic enters channel via membrane.
   - No use-dependence.

Question 12

What is conduction velocity?

Answer 12

Distance travelled by AP / time

Question 13

How is conduction velocity along an axon calculated?

Answer 13

Measure:

• distance between a stimulating electrode and a recording electrode
• time gap between stimulus and AP being registered by recording electrode

Question 14

What is the local current theory?

Answer 14

A change in MP in one part of an axon can immediately spread to adjacent areas because of local current spread.

Question 15

What is conduction velocity determined by?

Answer 15

• By how far along the axon local currents can spread.

- The further the local current spreads down the axon, the faster the conduction velocity of the axon will be.

Question 16

Which properties of the axon lead to a high conduction velocity?

Answer 16

1. High membrane resistance
2. Low membrane capacitance
3. Large axon diameter (leads to low cytoplasmic resistance)

Question 17

What does membrane resistance depend on? Why does a low membrane resistance limit the spread of local current?

Answer 17

• Depends on the number of open ion channels.
• Lower resistance = more open ion channel.
• Increased number of open ion channels limits spread of local current effect as slow-closing K+ channels cause current spread to decrease over time.

Question 18

What is membrane capacitance? Why does a high membrane capacitance limit the spread of local current?

Answer 18

• Ability to store charge.
• A high capacitance takes more current to charge (or a longer time for a given current) - decreases spread of local current.

Question 19

Why is very little ion flow required to generate an AP?

Answer 19

• Because of membrane capacitance.

- Each AP increases [Na+]i by only 40 uM (with resting [Na+]i = 10mM).