Generation of the

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Experimental Biology 2004
Cellular Homeostasis Refresher Course
Generation of the Membrane Potential
Stephen Wright University of Arizona
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The Starting Point Na,K-ATPase
3Na
ATP
3Na
2K
2K
Accounts for about 10 of basal metabolic rate!
1. The stoichiometry of a single cycle of
the Na,K-ATPase is 3 Na 2 K 1 ATP
2. At steady-state active fluxes of Na and
K balance the leak fluxes
3
in
out
4
in
out
100 K
(-)
()
K 10
Na 100
10 Na
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at Equilibrium
Electrical Force Chemical Force
(electrical voltage chemical gradient)
Nernst Equation
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Walther Hermann Nernst
Nobel Prize 1920
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R 8.31 J/(mol-deg) T 310o K F 96,500
coul/mol ln to log (x2.303)
Kin 100 mM and Kout 10 mM
VK ? -60 mV
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60 mV ? 10x gradient
So what?
i.e., Why should I care.?
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Well...
2. Provides a tool for predicting if active
transport processes are present...
3. Conceptual starting point for understanding
the physiological basis of all bioelectric
activity
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Summary to this point....
Chemical force and Electrical force are two
sides of the same coin
energy (driving forces)
Nernst equation displays the theoretical balance
between these forces
Goldman equation reflects the real
world situation of finite and variable ionic
permeabilities
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2 parameters of Goldman eq
Goldman Equation
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Factors influencing the Membrane Potential at Rest
Goldman prediction of Vm -84 mV
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(No Transcript)
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So, at rest PK dominates
What is the basis of PK?
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Ventricular Action Potential
Miake et al., JCI, 2003
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Then a medical student rose and said Speak
to us of Cl- w/apologies to Kahlil Gibran
The cell spends its energy building K and Na
gradients...
The Cl- gradient is largely a passive consequence
of the PD established by the K gradient/permeabili
ty
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ignoring Cl, the resting PD becomes a function
of the ratio of PNa to PK....
Vm
Vm closely tracks Kout except at very low
concentrations, or when PNa is relatively high
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In Conclusion...
A. Active transport establishes K and Na
gradients
these tend to be stable
B. Electrical Potential Difference is a
consequence of these gradients and the
relative permeability of the membrane to
these ions
C. At rest the PD is dominated by the combined
influence of
1. the outwardly direct K gradient 2. large PK