MnR S4 - Electrical Excitability

Question 1

What factors are action potentials dependant on?

Answer 1

Ion gradients and permeability of membrane

Question 2

What is the experimental evidence for Na+ being the primary cause of depolarisation?

Answer 2

Peak of action potential changes in manner parallel to changes in ENa

Question 3

How can voltage clamping be used to investigate mechanisms of action potential generation?

Answer 3

Controls membrane potential at set level so ionic current can be measured

Question 4

How does patch clamping differ from voltage clamping?

Answer 4

Patch clamping enables current flowing through individual ion channels to be measured

Question 5

What is the all or nothing principle with regards to generating an action potential generation?

Answer 5

Stimulus must cause depolarisation that reaches the threshold level or an action potential will not be generated

Question 6

Describe the process of an upstroke of an action potential

Answer 6

• Na+ channels open upon depolarisation to threshold
• Na+ enters the cell
• Membrane depolarises
• More Na+ channels open (positive feedback)

Question 7

Describe the process of a downstroke of an action potential

Answer 7

• Depolarisation
• Opens K+ channels causing K+ efflux
• Na+ channels become inactivated meaning Na+ influx stops
• Repolarisation

Question 8

What are the two phases of recovery after an action potential?

Answer 8

Absolute refractory period (ARP) - When nearly all Na+ channels are in the inactivated state

Relative refractory period (RRP) - When Na+ channels are recovering from inactivation, membrane excitability returns to normal as the number of the channels in the activated state decreases

Question 9

What is accommodation?

Answer 9

Longer lasting stimulus requires larger depolarisation to meet action potential threshold

Question 10

How does accommodation occur?

Answer 10

• Small number of Na+ channels open during long lasting stimulus and are inactivated
• Less Na+ channels then available to generate action potential
• Smaller action potential peak is reached
• Eventually length of time increases to a point that not enough Na+ channels are available to reach threshold for action potential firing

Question 11

Describe the structure of voltage gated Na+ channels

Answer 11

• Functional channel made up of one alpha subunit
• One peptide containing 4 homologous repeats
• Each repeat consists of 6 transmemiranous spanning domains
• S4 is made up of positive amino acid residues and is voltage sensitive

Question 12

How does the structure of K+ channels differ from Na+ channels?

Answer 12

Functional channel consists of 4 alpha sub units

Question 13

How do local anaesthetics work?

Answer 13

Block Na+ channels and prevent the stimulation of an action potential

Local anesthetic drugs bind more readily to sodium channels in an activated state, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade

Question 14

Describe the two pathways by which local anaesthetics

Answer 14

Hydrophobic - Not use dependant (pathway always available), lipid soluble so crosses the lipid bilayer and blocks channel. Ionised form cannot pass through.

Hydrophilic - Use dependant (pathway only available when channel open), pronated form of drug can pass through the open channel to block it. The more channels that are open the more are blocked

Question 15

How can conduction velocity be measured?

Answer 15

Calculated by measuring distance between extracellular stimulating electrode and recording electrode and the time between stimulus and action potential being registered by recording electrode

Question 16

Outline the relationship between conduction velocity and and fibre diameter

Answer 16

Myelinated nerve fibres - Velocity proportional to diameter

Unmyelinated nerve fibres - Velocity proportional to square root of diameter

Question 17

What is local current spread?

Answer 17

Change in membrane potential in one part can spread to adjacent parts of the membrane

Question 18

How can local current spread lead to subsequent action potentials?

Answer 18

Depolarisation in other parts of the axon meets threshold and generates action potential in that location

Question 19

What is fast conduction velocity (action potential) dependant on?

Answer 19

• High membrane resistance
• Low membrane capacitance
• Large axon diameter

Question 20

What is the length constant? (membrane conduction)

Answer 20

Distance taken for membrane potential to fall to 37% of its original value

Question 21

What is capacitance?

Answer 21

The ability to store charge, it is the property of the lipid bilayer

Question 22

What would be the effects of a high capacitance on local current?

Answer 22

More current to charge the membrane leading to decrease in spread of local current

Question 23

What is membrane resistance dependant on?

Answer 23

The number of ion channels open

Question 24

What would be the effects of a low membrane resistance on local current?

Answer 24

More ion channels open causes increased loss of local current which limits spread of local current effect

Question 25

List the two primary functions of the myelin sheath

Answer 25

• Increase membrane resistance

- Decrease capacitance

Question 26

How does saltatory conduction occur?

Answer 26

• Reduced capacitance in internodal (the myelin sheath bit, NOT gaps) region due to myelin sheath
• Local current induced by action potential at node of Ranvier spreads further down the axon to next node
• No action firing in the internodal region, only at nodes
• Local current spread is faster than action potential spread over axonal membrane surface causing an increase in conduction velocity

Question 27

What are the three possible consequences of demyelination of axons?

Answer 27

• Decreased conduction velocity
• Complete action potential block
• Only some action potentials transmitted