Previous lecture: three determinants of resting potential Major role for K + ions which is described by the Nernst equation This describes a true equilibrium Deviation from Nernst prediction due to Na + permeability Makes resting potential less negative Described by Goldman-Hodgkin-Katz equation Non-equilibrium: the cell would run down were it not for the Na + /K + ATPase The Na + /K + ATPase pumps more Na + out than K + in: makes resting potential more negative 1

Notes on the Purves chapter The Purves chapter has a few differences from the lectures when it explains/uses the GHK equation. Basic story is the same (and the maths are equivalent) – but differences in detail can be confusing. Please see the separate PDF file (in the resting potential section) for detailed explanation of the differences. 2

How is the action potential generated? Early finding: the inside becomes more positive during action potential (AP) Bernstein postulated that membrane selectivity breaks down: membrane can let all ions through This would predict membrane potential near zero at peak of AP (no selectivity  no potential) (Try working out E m using the GHK equation with P K = P Na !) 3

First action potential ever recorded: squid giant axon (Hodgkin & Huxley 1939) What really happens 4

“Overshoot” Membrane potential becomes positive at peak of AP The membrane is still selective... but not for K + It becomes selective for Na + 5

How would a Na + -selective membrane behave? Let’s suppose only Na + can move More Na + enters than leaves Inside becomes positive – + 6

This reduces Na + entry and increases efflux Inside becomes still more positive – + How would a Na + -selective membrane behave? 7

Equilibrium is reached Membrane potential is positive – mV Na + selectivity generates positive equilibrium potential How would a Na + -selective membrane behave? 8

Even if many ions are able to go through the membrane, there is one voltage where each individual ion will be at equilibrium (i.e. where influx = efflux) This is the equilibrium potential for that ion Can be predicted from the Nernst equation, exactly as if it were the only permeant ion So: Equilibrium potentials 9

+ – –85 mV Equilibrium potentials It doesn’t matter what the other ions are doing! 10

+ – –85 mV Equilibrium potentials It doesn’t matter what the other ions are doing! Sodium movement would be unequal at E K That would change the resting potential of the cell...but it doesn’t change the equilibrium potential for K +...E K is where influx and efflux of K + are equal, regardless of what other ions are doing 11

+ – –85 mV Equilibrium potentials It doesn’t matter what the other ions are doing! Sodium movement would be unequal at E K That would change the resting potential of the cell...but it doesn’t change the equilibrium potential for K +...E K is where influx and efflux of K + are equal, regardless of what other ions are doing Resting potential (of the whole cell) and equilibrium potential (of a single type of ion) are not the same thing 12

+34 mV Equilibrium potentials It doesn’t matter what the other ions are doing! 13

Evidence for the involvement of Na + Na + selectivity would explain the overshoot How could we test this?...by changing [Na + ] o You did this in the MEMPOT lab – now for the real experiment 14

Testing the hypothesis Prediction: if we reduce [Na + ] o, the overshoot should be reduced Tested by Hodgkin & Katz (1949) in squid axon Replaced sodium with sucrose or choline 15

Results just described suggest that increased Na + permeability (i.e. a lot of Na + channels opening transiently) underlies the action potential Goldman-Hodgkin-Katz (GHK) equation can describe it: Conclusions about the action potential 16

Results just described suggest that increased Na + permeability (i.e. a lot of Na + channels opening transiently) underlies the action potential Goldman-Hodgkin-Katz (GHK) equation can describe it: Conclusions about the action potential At rest: P K >>P Na so E m near to E K 17

Results just described suggest that increased Na + permeability (i.e. a lot of Na + channels opening transiently) underlies the action potential Goldman-Hodgkin-Katz (GHK) equation can describe it: Conclusions about the action potential During AP: P Na >>P K so E m near to E Na 18

Results just described suggest that increased Na + permeability (i.e. a lot of Na + channels opening transiently) underlies the action potential Goldman-Hodgkin-Katz (GHK) equation can describe it: Conclusions about the action potential At any time: E m depends on balance between P Na and P K 19

Conclusions about the action potential Permeabilities (or conductances) shown below Increased permeability = ion channels opening Na + channels open then later K + channels Increased K + permeability helps to end the AP 20

Defining some terms Depolarising, repolarising, hyperpolarising: all defined relative to resting potential Overshoot: defined relative to zero 21

Phases of the AP Depolarisation (“upstroke”) Peak Repolarisation Hyperpolarising afterpotential Overshoot 22

At rest: membrane permeable to K +, i.e. K + channels are open What ion channels are doing: The resting potential 23

What ion channels are doing: The action potential Na + channels open, Na + enters: depolarisation 24

What ion channels are doing: After the action potential Na + channels close, Na + entry stops, K + efflux increased: repolarisation 25

Conduction of the action potential Na + 26

Current through a single Na + channel from a human axon closed open –90 mV -60 mV Voltage (E m ) Current Depolarisation opens the channel: activation It closes again spontaneously: inactivation 27

Positive feedback during AP 28

...like an explosion 29

Reading for today’s lecture: Action potential Purves et al chapter 2 (page 37 onwards) Nicholls et al pages 26-31, 62-63, Kandel et al chapter 8

Next lecture: Axon types and functions; conduction in myelinated axons Reading for next lecture: Purves et al chapter 3 (page 49 onwards) Purves et al chapter 9 (pages ) Nicholls et al pages