M&R - Action Potential Flashcards
What are the three states voltage gated channels pass through on depolarisation?
Closed, open and inactivated
Why can a channel in the inactivated state not reopen?
What does this prevent?
It needs to be re-primed by repolarisation of the membrane.
Once inactivated, Na+ channel cannot be reopened during an AP
Irreversible depolarisation of the membrane, permits directionality to nerve impulse conduction and allows information to be coded with respect to the frequency in which APs are fired.
How does a wave of depolarisation progress over a cell membrane?
By the self reinforcing way Na+ channels open. The depolarising phase of an AP at one point on the cell membrane, by local current flow, will raise the membrane potential in adjacent regions of the membrane sufficiently to exceed the threshold for AP initiation in that region.
What occurs directly after the onset of an action potential?
What occurs after that?
Absolute refractory period - the membrane cannot be further excited
Relative refractory period - becomes progressively easier to elicit a further action potential as the Na+ channels recover from inactivation
What do action potentials do to the voltage across the membrane? And what does it depend on?
When do action potentials occur?
Change the voltage across membranes which depends on ionic gradients and relative permeability
If a threshold level is reached
How are action potentials generated?
By an increase in permeability to Na+
Bringing the permeability close to the Na+ equilibrium ENa
How can you measure the effect of changes of membrane potential on sodium and potassium currents?
Describe.
Technique called voltage clamp
Membrane potential is controlled and the currents flowing through membrane are measured.
Much clearer measurement of the effect of voltage on the number of Na+ and K+ channels open at different membrane potentials.
Both channels are voltage gated –> depolarisation will cause them to open
What is inactivation of Na+ channels and when does it occur?
During maintained depolarisation
Na+ channels close by inactivation
Describe what happens during the upstroke (depolarisation) of AP
What type of feedback is this?
Depolarisation to threshold
Na+ channels open
Na+ enters the cell
Membrane depolarises
Positive feedback
What channels are involved in repolarisation and what happens to them?
Na+ channels - inactivation
K+ channels activated
What is important about the Na+/K+ pump in action potentials?
It is NOT involved in repolarisation
It sets the concentration gradients
When can Na+ channels recover?
When the membrane potential has returned to its resting level
What happens to the Na+ channels in the absolute refractory period (ARP) and the Relative Refractory Period (RRP)?
ARP - nearly all Na+ channels are in the inactivated state
RRP - Na+ channels are recovering from inactivation, the excitability returns towards normal as the number of channels in the inactivated state decreases
Describe the molecular nature of Na+ and Ca2+ channels
How many transmembrane spanning domains are in one repeat?
Their main pore forming subunit is one peptide consisting of 4 homologous repeats.
Each repeat consists of 6 transmembrane spanning domains with one of these domains being able to sense the voltage field across the membrane.
Give an example of a local anaesthetic and describe the way it stops an action potential being generated?
Procaine
Binds to and blocks Na+ channels –> stops action potential generation
In what order to local anaesthetics block conduction in nerve fibres?
How do they work?
Small myelinated axons
Non myelinated axons
Large myelinated axons
They are weak bases and cross the membrane in their unionised form.
They block Na+ channels easier when the channel is open and have a higher affinity to the inactivated state of the Na+ channel
If the conductance ion is increased, what happens to the membrane potential?
It will move closer to the equilibrium potential
What are three ways to investigate the mechanism of action potential generation?
Voltage clamping controls - controls the membrane potential so ionic currents can be measured
Different ionic concentrations - contribution of various ions can be assessed
Patch clamping - enables currents flowing through individual ion channels to be measured
What is the difference between the Na+ and K+ channels?
Na+ activated quickly and deactivate
K+ do not deactivate and close slowly
Describe the time course of conductance changes of Na+ and K+ during an action potential?
Na+ rapid increase and undergo inactivation
K+ open wth depolarisation more slowly and they close more slowly
Where in a neutron is an action potential initiated?
And why?
Axon hillock - there are lots of voltage gated Na+ channels there
Depolarisation to threshold initiates action potential
What is Accomodation?
H
If you require a long stimulus, how much depolarisation would you require?
Large depolarisation to initiate an action potential.
Threshold curve. Further away the distance, more AP needed for it to be carried for longer
What is an inactivation particle?
When a pore is closed, it sits there.
When the pore is open, the inactivated particle swings into the pore and blocks it. When that is occupying the pore, any flow through the channel is blocked and before it can open again it will need to recover.
What membrane spanning domain detected the voltage field?
What is responsible for producing the conformational change in voltage gated ion channels?
S4 - has a high number of positively charged amino acids in it which contributes to voltage sensitivity
The change in voltage field which alters the force which is detected
What region of the K+ channel contributes to pore selectivity?
P (or H5)
Why are action potentials described as all or nothing?
Because there is a threshold for initiation
Why does the membrane become hyperpolarised?
How is it corrected?
The K+ channels open and close very slowly - too much K+ diffuses out
Corrected - Na+ and K+ diffuse through the membrane down the concentration gradient. Na+/K+ pump also helps - brings the membrane potential back up to resting potential
What is the upstroke of the action potential due to?
Inward movement of Na+ ions into the cell
Does the number of voltage insensitive K+ channels that are open change during initiation of an action potential?
No
What do Na+ blocking drugs e.g. Tetrodotoxin cause?
Block the firing of action potentials
What happens to the permeability of Na+ and K+ during initiation of an action potential?
Na+ permeability of the membrane becomes much higher than that of K+
During the peak of an action potential what happens to the Na+ channels?
Move into an inactivated conformation to reduce Na+ influx
When may Na+ channels re-open?
After repolarisation of the membrane and a change in the conformation from the inactivated to closed state
What happens to the Na+ channels during the falling peak of the action potential?
Remain largely inactivated
What happens to the membrane permeability of K+ during the falling peak of the action potential?
Membrane permeability to K+ continues to rise due to the continued slow activation of voltage sensitive K+ channels
What happens to the Na+ channels during the hyperpolarising phase at the end of a nerve action potential?
Majority of Na+ channels return to the closed state and are ‘re-primed’ for opening
Can a second action potential be fired during the hyperpolarising phase?
Yes
How is the resting membrane potential restored during the hyperpolarising phase?
Restored away from the equilibrium potential for K+ due to the minor leak of ions through the membrane with positive equilibrium potentials
Can another nerve fire an action potential during the absolute refractory period in nerve cells?
No, it is impossible
What needs to happen to the stimulus in order to fire during the relative refractory period?
Nerve cell requires a stronger stimulus that usual
Why is the threshold for firing an action potential raised during the relative refractory period?
Some Na+ channels are inactivated as a result of an action potential that has just fired.
Why do nerve fibres with greater diameter conduct nerve impulses with greater velocity?
Due to the reduced resistance to local current flow as a result of the relative abundance of ionic species within the axoplasm
What is the name of the period that prevents reversal of the nerve impulse being conducted along a nerve?
Absolute refractory period
