M&R S4 - Electrical Excitability Flashcards
What is an action potential?
A change in voltage across a membrane
What factors are involved in the creation of an action potential?
Ionic gradient across the membrane
Relative permeability of the membrane
What is meant by “Action potentials are all or nothing”
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
What happens to the amplitude of an action potential as it propagates?
It propagates with no loss of amplitude
Describe how a membrane becomes fully depolarised during an action potential.
“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)
When a cell becomes depolarised during an action potential, how is repolarisation achieved?
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.
What is the absolute refractory period and when does it occur?
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
What is the relative refractory period and when does it occur?
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
Describe ‘Accommodation’
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.
Describe the important molecular features of voltage gated Na+ and Ca2+ channels.
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.
How do voltage gated K+ channels differ from voltage gated Na+ and Ca2+ channels?
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.
Describe the action of local anaesthetics and give an example
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
Local anaesthetics action on different types of nerve fibre is slightly different, describe this difference and briefly explain the consequences
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
How can an action potential be generated via electrical stimulation of the nerve fibre in the lab?
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
How can conduction velocity of a nerve fibre be tested?
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
How is an action potential conducted along an axon?
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)
How is conduction velocity determined?
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)
What is the ‘length constant’ in terms of electrical propagation?
The distance it takes for the potential across a membrane to fall to 37% of its original value
Why does high membrane resistance increase conduction velocity?
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
Why does large axon diameter increase conduction velocity?
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
Why does low membrane capacitance increase conduction velocity?
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
Why is an action potential incapable of propagating backwards?
The area immediately ‘behind’ a propagating action potential has very low electrical excitability due to inactivated Na+ channels
How does myelination of a neurone affect conduction velocity
Increases conduction velocity by:
Increasing membrane resistance ~100x
Decreasing membrane capacitance ~100x
Hence increasing conduction velocity
How does the presence of nodes of ranvier affect AP conduction?
Describe an important feature of the cell membranes at the nodes of ranvier
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)
Myelination doesn’t always increase conduction velocity, explain.
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
What is the max conduction velocity of an unmyelinated and myelinated nerve?
Velocity in nerves is proportional to what in each case?
Unmyelinated = ~20ms-1
Velocity is proportional to square root of diameter
Myelinated = ~120ms-1
Velocity is proportional to diameter
What is the optimum Axon diameter to myelin diameter ratio?
Axon diameter/myelin diameter = 0.7
What cells form myelin? (TOB)
Schwann cells in the PNS
Oligodendrocytes in the CNS
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
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
When does myelination occur?
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
