M&R - Action Potential Flashcards

1
Q

What are the three states voltage gated channels pass through on depolarisation?

A

Closed, open and inactivated

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2
Q

Why can a channel in the inactivated state not reopen?

What does this prevent?

A

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.

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3
Q

How does a wave of depolarisation progress over a cell membrane?

A

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.

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4
Q

What occurs directly after the onset of an action potential?

What occurs after that?

A

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

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5
Q

What do action potentials do to the voltage across the membrane? And what does it depend on?

When do action potentials occur?

A

Change the voltage across membranes which depends on ionic gradients and relative permeability

If a threshold level is reached

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6
Q

How are action potentials generated?

A

By an increase in permeability to Na+

Bringing the permeability close to the Na+ equilibrium ENa

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7
Q

How can you measure the effect of changes of membrane potential on sodium and potassium currents?

Describe.

A

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

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8
Q

What is inactivation of Na+ channels and when does it occur?

A

During maintained depolarisation

Na+ channels close by inactivation

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9
Q

Describe what happens during the upstroke (depolarisation) of AP

What type of feedback is this?

A

Depolarisation to threshold

Na+ channels open
Na+ enters the cell
Membrane depolarises

Positive feedback

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10
Q

What channels are involved in repolarisation and what happens to them?

A

Na+ channels - inactivation

K+ channels activated

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11
Q

What is important about the Na+/K+ pump in action potentials?

A

It is NOT involved in repolarisation

It sets the concentration gradients

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12
Q

When can Na+ channels recover?

A

When the membrane potential has returned to its resting level

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13
Q

What happens to the Na+ channels in the absolute refractory period (ARP) and the Relative Refractory Period (RRP)?

A

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

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14
Q

Describe the molecular nature of Na+ and Ca2+ channels

How many transmembrane spanning domains are in one repeat?

A

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.

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15
Q

Give an example of a local anaesthetic and describe the way it stops an action potential being generated?

A

Procaine

Binds to and blocks Na+ channels –> stops action potential generation

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16
Q

In what order to local anaesthetics block conduction in nerve fibres?

How do they work?

A

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

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17
Q

If the conductance ion is increased, what happens to the membrane potential?

A

It will move closer to the equilibrium potential

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18
Q

What are three ways to investigate the mechanism of action potential generation?

A

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

19
Q

What is the difference between the Na+ and K+ channels?

A

Na+ activated quickly and deactivate

K+ do not deactivate and close slowly

20
Q

Describe the time course of conductance changes of Na+ and K+ during an action potential?

A

Na+ rapid increase and undergo inactivation

K+ open wth depolarisation more slowly and they close more slowly

21
Q

Where in a neutron is an action potential initiated?

And why?

A

Axon hillock - there are lots of voltage gated Na+ channels there

Depolarisation to threshold initiates action potential

22
Q

What is Accomodation?

A

H

23
Q

If you require a long stimulus, how much depolarisation would you require?

A

Large depolarisation to initiate an action potential.

Threshold curve. Further away the distance, more AP needed for it to be carried for longer

24
Q

What is an inactivation particle?

A

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.

25
Q

What membrane spanning domain detected the voltage field?

What is responsible for producing the conformational change in voltage gated ion channels?

A

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

26
Q

What region of the K+ channel contributes to pore selectivity?

A

P (or H5)

27
Q

Why are action potentials described as all or nothing?

A

Because there is a threshold for initiation

28
Q

Why does the membrane become hyperpolarised?

How is it corrected?

A

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

29
Q

What is the upstroke of the action potential due to?

A

Inward movement of Na+ ions into the cell

30
Q

Does the number of voltage insensitive K+ channels that are open change during initiation of an action potential?

A

No

31
Q

What do Na+ blocking drugs e.g. Tetrodotoxin cause?

A

Block the firing of action potentials

32
Q

What happens to the permeability of Na+ and K+ during initiation of an action potential?

A

Na+ permeability of the membrane becomes much higher than that of K+

33
Q

During the peak of an action potential what happens to the Na+ channels?

A

Move into an inactivated conformation to reduce Na+ influx

34
Q

When may Na+ channels re-open?

A

After repolarisation of the membrane and a change in the conformation from the inactivated to closed state

35
Q

What happens to the Na+ channels during the falling peak of the action potential?

A

Remain largely inactivated

36
Q

What happens to the membrane permeability of K+ during the falling peak of the action potential?

A

Membrane permeability to K+ continues to rise due to the continued slow activation of voltage sensitive K+ channels

37
Q

What happens to the Na+ channels during the hyperpolarising phase at the end of a nerve action potential?

A

Majority of Na+ channels return to the closed state and are ‘re-primed’ for opening

38
Q

Can a second action potential be fired during the hyperpolarising phase?

A

Yes

39
Q

How is the resting membrane potential restored during the hyperpolarising phase?

A

Restored away from the equilibrium potential for K+ due to the minor leak of ions through the membrane with positive equilibrium potentials

40
Q

Can another nerve fire an action potential during the absolute refractory period in nerve cells?

A

No, it is impossible

41
Q

What needs to happen to the stimulus in order to fire during the relative refractory period?

A

Nerve cell requires a stronger stimulus that usual

42
Q

Why is the threshold for firing an action potential raised during the relative refractory period?

A

Some Na+ channels are inactivated as a result of an action potential that has just fired.

43
Q

Why do nerve fibres with greater diameter conduct nerve impulses with greater velocity?

A

Due to the reduced resistance to local current flow as a result of the relative abundance of ionic species within the axoplasm

44
Q

What is the name of the period that prevents reversal of the nerve impulse being conducted along a nerve?

A

Absolute refractory period