M&R S4 - Electrical Excitability

Question 1

What is an action potential?

Answer 1

A change in voltage across a membrane

Question 2

What factors are involved in the creation of an action potential?

Answer 2

Ionic gradient across the membrane

Relative permeability of the membrane

Question 3

What is meant by “Action potentials are all or nothing”

Answer 3

Na+ channels are voltage gated and when they open cause depolarisation

This depolarisation leads to more Na+ channels opening

This process cannot be stopped halfway, all Na+ channels WILL open.

This means, once threshold depolarisation is reached, a full action potential will result

If threshold depolarisation is not reached, there is no action potential

Question 4

What happens to the amplitude of an action potential as it propagates?

Answer 4

It propagates with no loss of amplitude

Question 5

Describe how a membrane becomes fully depolarised during an action potential.

Answer 5

“The Sodium Hypothesis”

Once the membrane is depolarised to threshold, voltage gated Na+ channels open

Na+ influx into the cell

Na+ ions attempt to move to their equilibrium potential (+61mV)

This influx depolarises the membrane further causing more Na+ channels to open and cause even more depolarisation. (This is a good example of positive feedback)

Question 6

When a cell becomes depolarised during an action potential, how is repolarisation achieved?

Answer 6

During maintained depolarisation Na+ channels close via a mechanism called ‘inactivation’

Voltage gated K+ channels are opened by the depolarisation, causing K+ efflux from the cell as K+ ions attempt to move to their equilibrium potential (-88mV)

A combination of these two events leads to repolarisation.

Question 7

What is the absolute refractory period and when does it occur?

Answer 7

The ARP occurs once nearly all Na+ channels have been opened and subsequently inactivated

During this period electrical excitability of the membrane is at 0

Question 8

What is the relative refractory period and when does it occur?

Answer 8

The RRP occurs as Na+ channels are recovering from inactivation. The excitability slowly returns to normal as the number of channels in the inactivated state decreases

Question 9

Describe ‘Accommodation’

Answer 9

The longer a stimulus is, the larger the depolarisation is necessary to initiate an action potential.

This is because some Na+ channels become inactivated during the longer period of depolarisation before threshold voltage is reached, hence raising the threshold.

Question 10

Describe the important molecular features of voltage gated Na+ and Ca2+ channels.

Answer 10

Their main pore forming subunit is one peptide consisting of:

4 homologous repeats

Each repeat consisting of 6 transmembrane domains

One of these domains (Domain 4) can sense voltage across the membrane

The pore region (H5 region) is found between the 5th and 6th transmembrane domains

Contains an ‘inactivation particle’ which will close the gate when the membrane becomes depolarised

The function of the pore requires only one subunit.

Question 11

How do voltage gated K+ channels differ from voltage gated Na+ and Ca2+ channels?

Answer 11

They are very similar in structures, The difference is that one pore is made up of 4 peptides, instead of 4 homologous repeats in the same peptide.

Question 12

Describe the action of local anaesthetics and give an example

Answer 12

Act via binding to and blocking Na+ channels, thereby stopping action potential generation

They block open Na+ channels but also have a higher affinity for the inactivated state

They are weak bases that cross the membrane in their unionized form

An example is Procaine

Question 13

Local anaesthetics action on different types of nerve fibre is slightly different, describe this difference and briefly explain the consequences

Answer 13

They block conduction in different nerve fibres in the following order

First, Small myelinated axons

Then Non-myelinated axons

Then Large myelinated axons

Because of this they tend to effect sensory neurones before motor neurones

Question 14

How can an action potential be generated via electrical stimulation of the nerve fibre in the lab?

Answer 14

An anode and cathode are places across the nerve fibre and a current is run through, under the anode excitability will be reduced, but under the cathode it will increase.

Stimulation in this manner that reaches threshold results in an artificially generated action potential that will propagate down the nerve

Question 15

How can conduction velocity of a nerve fibre be tested?

Answer 15

An artificial action potential can be generated and extracellular recording electrodes are placed downstream

Conduction velocity

=

Distance between stimulating and recording electrodes

Divided by

Time taken to travel between

Question 16

How is an action potential conducted along an axon?

Answer 16

A change in membrane potential produces transmembrane currents in neighbouring regions

As Na+ channels are voltage gated this opens channels in these neighbouring regions and the action potential propagates (providing threshold voltage is reached)

Question 17

How is conduction velocity determined?

Answer 17

How far the local current can spread along an axon determines conduction velocity

This in turn is determined by some properties of the axon, including:

High membrane resistance

Low membrane capacitance

Large axon diameter (leading to low cytoplasmic resistance)

Question 18

What is the ‘length constant’ in terms of electrical propagation?

Answer 18

The distance it takes for the potential across a membrane to fall to 37% of its original value

Question 19

Why does high membrane resistance increase conduction velocity?

Answer 19

Ohms Law V = IR states that the higher the resistance the higher the potential difference across it

More voltage across the membrane means more Na+ channels open making it easier to fire an AP, increasing conduction velocity

Question 20

Why does large axon diameter increase conduction velocity?

Answer 20

Ohms law I = V/R states that the lower the resistance (in this case, lower cytoplasmic resistance from the larger diameter) the larger the current.

Therefore the action potential will travel further and conduction velocity is increased

Question 21

Why does low membrane capacitance increase conduction velocity?

Answer 21

Capacitance is the ability to store charge

Therefore a membrane withe a low capacitance will take less current to charge (or a shorter time for a given current).

This increases conduction velocity

Question 22

Why is an action potential incapable of propagating backwards?

Answer 22

The area immediately ‘behind’ a propagating action potential has very low electrical excitability due to inactivated Na+ channels

Question 23

How does myelination of a neurone affect conduction velocity

Answer 23

Increases conduction velocity by:

Increasing membrane resistance ~100x

Decreasing membrane capacitance ~100x

Hence increasing conduction velocity

Question 24

How does the presence of nodes of ranvier affect AP conduction?

Describe an important feature of the cell membranes at the nodes of ranvier

Answer 24

Myelination allows saltatory conduction, where the Ap jumps between nodes of ranvier

This is because the myelin sheath acts as a good insulator causing the local circuit currents to depolarise the next node above threshold

These nodes have a high density of Na+ channels in contrast to unmyelinated neurones that have a more even distribution (~10,000 per node)

Question 25

Myelination doesn’t always increase conduction velocity, explain.

Answer 25

Small diameter axons such as sensory neurones are not myelinated as myelination slows conduction velocity of axons under 1mm diameter

Large diameter axons such as in motor neurones are myelinated as this increases conduction velocity in axons above 1mm diameter

Question 26

What is the max conduction velocity of an unmyelinated and myelinated nerve?

Velocity in nerves is proportional to what in each case?

Answer 26

Unmyelinated = ~20ms-1
Velocity is proportional to square root of diameter

Myelinated = ~120ms-1
Velocity is proportional to diameter

Question 27

What is the optimum Axon diameter to myelin diameter ratio?

Answer 27

Axon diameter/myelin diameter = 0.7

Question 28

What cells form myelin? (TOB)

Answer 28

Schwann cells in the PNS

Oligodendrocytes in the CNS

Question 29

What are the consequences of demyelination of an axon?

Give an example of a disease in which this happens along with a brief description of the disease

Answer 29

Can lead to decreased conduction velocity, complete or partial block of APs

Multiple Sclerosis

Auto immune disease where myelin is destroyed in certain areas of the CNS and replaced with scar tissue

Question 30

When does myelination occur?

Answer 30

Production of myelin begins in the 14th week of development

Little myelin exists in the brain at the time of birth, it develops throughout infancy and on into the adolescent years