Lecture 4 - Action potentials

Question 1

Conductance of an ion across the membrane depends on …

Answer 1

Permeability (ion channels)

Equilibrium potential (driving force)

Conductance is the inverse of electrical resistance. If the conductance of the membrane to a particular ion is low, then the resistance to movement of that ion across the membrane is high.

Question 2

Vm

Answer 2

Membrane potential - at the top of the action potential the membrane potential is reaching the equilibrium potential for sodium

Question 3

GNa+

Answer 3

Na+ conductance - at rest, there is very little conductance of sodium, as the action potential starts the conduction of sodium goes up remarkably and then comes back down to just about zero - the sodium will depolarise the cell as it comes in

Question 4

GK+

Answer 4

Potassium conductance - potassium conductance also rises more slowly and not to such a great extent but also lasts much longer, potassium we repolarise and hyper polarise the cell as it goes out

Question 5

Voltage gated Na+ channels

Answer 5

Activation gate (voltage sensor) - the ‘on’ switch

Selectivity filter - specific for Na+

Inactivation gate - actively closed - the ‘off’ switch

Blocked by tetrodotoxin - from the puffer fish (binds irreversibly to the channel pore and block it)

When the sodium can flow through, it is flowing down its electrochemical gradient from outside to inside

Made up of two beta subunits and four alpha subunits

Question 6

Subunits of Na+ channels

Answer 6

2 beta subunits and 4 alpha subunits

Question 7

Inactivation gate

Answer 7

Inactivation gate - ‘ball and chain’ model

The inactivation gate is part of an intracellular loop

Question 8

Not activated Na+ voltage gated channel

Answer 8

Not activated = pore closed - positive charge in the way therefore deflects the positive charge on the sodium (note: not activated is not the same as inactivated)

Question 9

Activated Na+ voltage gated channel

Answer 9

Activated = pore open - positive charge nearby for selectivity - Something causes the voltage to become depolarised sufficiently to reach threshold and this voltage change moves the positive charges and opens the gate which allows for sodium to come through down its electrochemical gradient into the cell allowing for a larger depolarisation which is known as an action potential

Question 10

Inactivated Na+ voltage gated channel

Answer 10

pore still open - but ball on the end of the chain blocks it

Later in the action potential the inactivation gates close - pore still open but the ball on the end of the chain has essentially plugged the sodium channel from the inside

The ball and chain is activated by a voltage change as well - the ball and chain responds more slowing to the charge than the activation gate so the not activated state opens more quickly and the inactivated state closes more slowly

Not activated is closed, inactivated is open but locked from the inside but in both cases the sodium cannot enter the cell

Question 11

Voltage-gated K+ channels

Answer 11

Activation gate
Selectivity filter - specific for K+
Inactivation gate - slower than for voltage-gated Na+ channel
Blocked by tetraethylammonium

Question 12

Voltage gated Na+ channels are blocked by

Answer 12

tetrodotoxin - from the puffer fish (binds irreversibly to the channel pore and block it)

Question 13

Voltage gated K+ channels are blocked by

Answer 13

tetraethylammonium

Question 14

Absolute refractory period

Answer 14

No action potential is possible

Question 15

Relative refractory period

Answer 15

Action potential is possible but more difficult to initiate

Question 16

Channel gating during the action potential

Answer 16

Large increase in sodium conductance at the beginning of the action potential which quickly comes back down to resting values again and then for potassium conductance there is a slower increase and a lower maximum which more slowly comes back down to base line again

At RMP, the activation gates for sodium and potassium are closed therefore no conductance through these channels at rest

(1) = Something happens that brings the membrane potential to threshold causing the opening of the sodium channels which is the threshold for the initiation of the action potential so the Na+ channels open which allows for Na+ to flow into the cell and the conductance of sodium increases, positive charge moving in therefore causes depolarisation which causes the depolarising stage of the action potential and the potassium channels are still shut there have pretty much zero conductance at this stage
(2) = Next stage, the sodium channel is still open and it is not inactivated but the potassium channel is open so you have sodium flowing in causing depolarisation and now it is opposed by potassium flowing our causing a hyper polarisation so now you have ion leaving in two opposite directions across the membrane trying to cancel each other out, initially sodium wins but that eventually turns into potassium winning so the voltage repolarises towards the resting membrane potential
(3) = Absolute refractory period means that sodium can no longer cross the membrane so there is only potassium channels that is open although the conductance is going down so some of them are closing but not all of them. WIth the sodium channels closed and the potassium channels open you get a net efflux of potassium which causes the afterhyperpolarisation below the RMP (since K+ channels are open for a bit longer than Na+ channels). Next the sodium channel inactivation gate is already closed therefore there is no net flow of sodium but there is still flow of potassium so afterhyperpolarisation continues
(4) = Relative refractory period means that the inactivation gate of sodium is open again, the potassium channel is still open so potassium can still flow out so still get after hyper polarisation past RMP therefore it is more difficult to excite the cell to threshold

Eventually everything goes back to the resting configuration

Question 17

axonal adaptations that increase action potential conduction velocity and explain how they do so

Answer 17

bigger allows faster flow (larger axons), insulation (myelin sheath) reduces leakage

Question 18

Ideal values for increasing conduction…

Answer 18

Ideal for increasing conduction = decrease rin (internal resistance), increase rm (membrane resistance)

Question 19

Membrane resistance (rm)

Answer 19

Forcing more ions to flow inside the axon by allowing less to cross the membrane which is increasing membrane resistance will also increase the condition

Increase axon insulation i.e. myelin increases membrane resistance (this also decreases the presence of the channels through which ions can flow, reduce leakage)

Question 20

Axial (internal) resistance (rin)

Answer 20

Increase in axon diameter, decreases axial resistance which allows more ions to readily flow and as you increase the diameter you get an increase in the conduction velocity

Question 21

Myelination

Answer 21

High density of sodium channels at the Nodes of Ranvier, but no channels at the internodes (in between the nodes i.e. the myelin)

Schwann cell provides the myeline in the PNS, essentially the Schwann cells are glia that have a long sheet process which is wrapped around and around the axon which provides electrical insulation around the icon and even if you had sodium/potassium channels here there is essentially an absence of extracellular fluid for any sodium or potassium to move in or out

Cannot insulate the whole vessel as generation of the action potential has to occur therefore there are nodes

Question 22

Saltatory conduction

Answer 22

Saltatory conduction between nodes of ranvier (jumping from point to point)

Nodes have sodium and potassium channels and this is where the ion conductance happens across the membrane to get an action potential to occur

The distance between the nodes is sufficient so that when the charge reaches the next node of ranvier it is sufficient to bring the next node to threshold and trigger an action potential in this node as well

Since the currents in the internode are just travelling along the inside of the pipe, this process is just fast diffusion through the pipe rather than all of the mechanical opening and closing that is required for the action potential to occur, this just pushes the ions along their concentration gradients which is what a local current is