previous lecture: three determinants of resting potential major role for k + ions which is described...
TRANSCRIPT
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
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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.
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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 zeroat peak of AP (no selectivityno potential)(Try working out Em using the GHK equation with PK = PNa!)
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First action potential ever recorded:squid giant axon(Hodgkin & Huxley 1939)
What really happens
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What really happens
•“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
– +
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•This reduces Na+ entry and increases efflux•Inside becomes still more positive
– +– +
How would a Na+-selective membrane behave?
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•Equilibrium is reached•Membrane potential is positive
– +– +– +
+34 mV
•Na+ selectivity generates positive equilibrium potential
How would a Na+-selective membrane behave?
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•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
i
oK ]K[
]K[ln
zF
RTE
i
oNa ]Na[
]Na[ln
zF
RTE
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+ –+ –+ –
–85 mV–85 mV
Equilibrium potentialsIt doesn’t matter what the other ions are doing!
mV85mM90
mM3ln
]K[
]K[ln
i
oK
zF
RT
zF
RTE
10
+ –+ –+ –
–85 mV–85 mV
Equilibrium potentialsIt doesn’t matter what the other ions are doing!
mV85mM90
mM3ln
]K[
]K[ln
i
oK
zF
RT
zF
RTE
•Sodium movement would be unequal at EK
•That would change the resting potential of the cell•...but it doesn’t change the equilibrium potential for K+
•...EK is where influx and efflux of K+ are equal, regardless of what other ions are doing
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+ –+ –+ –
–85 mV–85 mV
Equilibrium potentialsIt doesn’t matter what the other ions are doing!
mV85mM90
mM3ln
]K[
]K[ln
i
oK
zF
RT
zF
RTE
•Sodium movement would be unequal at EK
•That would change the resting potential of the cell•...but it doesn’t change the equilibrium potential for K+
•...EK 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
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+34 mV
Equilibrium potentialsIt doesn’t matter what the other ions are doing!
mV34mM30
17mM1ln
]Na[
]Na[ln
i
oNa
zF
RT
zF
RTE
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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
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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
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•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
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iNaiK
oNaoKm ]Na[]K[
]Na[]K[ln
PP
PP
zF
RTE
iNaiK
oNaoKm ]Na[]K[
]Na[]K[ln
PP
PP
zF
RTE
•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: PK>>PNa
•so Em near to EK
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iNaiK
oNaoKm ]Na[]K[
]Na[]K[ln
PP
PP
zF
RTE
•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: PNa>>PK
•so Em near to ENa
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•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:•Em depends on balance between PNa and PK
iNaiK
oNaoKm ]Na[]K[
]Na[]K[ln
PP
PP
zF
RTE
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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
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Defining some terms
•Depolarising, repolarising, hyperpolarising:all defined relative to resting potential•Overshoot: defined relative to zero
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Phases of the AP
Depolarisation(“upstroke”)
Peak
Repolarisation
Hyperpolarising afterpotential
Overshoot
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At rest: membrane permeable to K+,i.e. K+ channels are open
What ion channels are doing:The resting potential
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What ion channels are doing:The action potential
Na+ channels open, Na+ enters: depolarisation
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What ion channels are doing:After the action potential
Na+ channels close, Na+ entry stops, K+ efflux increased: repolarisation
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Conduction of the action potential
Na+ Na+ Na+ Na+ Na+ Na+
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Current through a single Na+ channel from a human axon
closed
open
–90 mV
-60 mVVoltage (Em)
Current
Depolarisation opens the channel:activation
It closes again spontaneously:inactivation
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Positive feedback during AP
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...like an explosion
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Reading for today’s lecture:
Action potential•Purves et al chapter 2 (page 37 onwards)•Nicholls et al pages 26-31, 62-63, 91-93
•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 189-194)
•Nicholls et al pages 121-126