Generation of resting membrane potential
Stephen H. Wright
Department of Physiology, College of Medicine, University of Arizona, Tucson,
Arizona 85724
IT WOULD BE DIFFICULT TO EXAGGERATE the physiological significance of the
transmembrane electrical potential difference (PD). This gradient of electrical
energy that exists across the plasma membrane of every cell in the body
influences the transport of a vast array of nutrients into and out of cells, is a key
driving force in the movement of salt (and therefore water) across cell membranes
and between organ-based compartments, is an essential element in the signaling
processes associated with coordinated movements of cells and organisms, and is
ultimately the basis of all cognitive processes. For those reasons (and many more),
it is critical that all students of physiology have a clear understanding of the basis
of the resting membrane potential (so called to distinguish the steadystate
electrical condition of all cells from the electrical transients that are the “action
potentials” of excitable cells: i.e., neurons and muscle cells). How, then, does this
electrical gradient arise? It is the consequence of the influence of two physiological
parameters: 1) the presence of large gradients for K+ and Na+ across the plasma
membrane; and 2) the relative permeability of the membrane to those ions. The
gradients for K+ and Na+ are the product of the activity of the Na+-K+-ATPase, a
primary active ion pump that is ubiquitously expressed in the plasma membrane of
(for all intents and purposes) all animal cells. This process develops and then
maintains the large outwardly directed K+ gradient, and the large inwardly directed
Na+ gradient, that are hallmarks of animal cells. For the purpose of this discussion,
we will assume that the requisite gradients are in place (acknowledging that the
mechanism of ion transport is beyond the scope of this presentation).
The second parameter, the relative permeability of the plasma membrane to Na +
and K+, reflects the open versus closed status of ion-selective membrane
channels. Importantly, cell membranes display different degrees of permeability to
different ions (i.e., “permselectivity”), owing to the inherent selectivity of specific ion
channels. The combination of 1) transmembrane ion gradients, and 2) differential
permeability to selected ions, is the basis for generation of transmembrane voltage
differences. This idea can be developed by considering the hypothetical situation of
two solutions separated by a membrane permselective to a single ionic species.
Side 1 (the “inside” of our hypothetical cell) contains 100 mM KCl and 10 mM NaCl.
Side 2 (the “outside”) contains 100 mM NaCl and 10 mM KCl. In other words, there
is an “outwardly directed” K+ gradient, and inwardly directed Na+ gradient, and no
transmembrane gradient for Cl-. For the purpose of this discussion, this ideal
permselective membrane is permeable only to K+.
The electrochemical driving force (ECDF).
Membrane potential (Vm) is the separation of charges across a cell membrane and
is established by the selective permeability of the membrane and the active
transport of ions across it. The result is a differential distribution of ions and an
excess of negative charge on the membrane’s inner surface. For any ion, X,
present in unequal concentrations across the membrane, there are two forces
acting on it. First, there is a chemical driving force (CDF) resulting from the
concentration gradient. Second, there is an electrical driving force (EDF) resulting
from the interaction between the charge of the ion and Vm. If these forces are
equal in magnitude but opposite in direction, there will be no net, or
electrochemical, driving force acting on that ion (Fig. 1A). Under these conditions,
ion X will be in electrochemical equilibrium and will exhibit no net flux in either
direction across the membrane. The membrane potential that exactly balances the
CDF, thus establishing electrochemical equilibrium, is obtained from the Nernst
equation
E x = (RT/zF)ln(Xe/Xi)
where Ex is the equilibrium potential for ion X, R is the gas constant, T is the
absolute temperature, z is the valance of ion X, F is the Faraday constant, Xe the
extracellular concentration of X, and Xi the intracellular concentration of X.
Converting to log base 10 for a monovalent ion at 18C, the Nernst equation
reduces to
E x = 58 log(Xe/Xi)
If Vm does not equal Ex, then X will be out of electrochemical equilibrium and there
will exist an ECDF equal in magnitude to the difference between Vm and E x
(ECDF)x = Vm - Ex
This will result in a net passive flux of X across the membrane in the same
direction as the ECDF (Fig. 1B). Thus X will carry current, Ix, across the membrane
in accordance with a modified version of Ohm’s law
Ix = gx(Vm - Ex)
where g, is the membrane conductance for ion X.
In the steady state, when the cell is not signaling (i.e., at resting Vm), the
concentration gradients of ions that are not in electrochemical equilibrium and that,
therefore, exhibit net passive flux across the membrane, are maintained by active
transport. Thus the passive flux of an ion in one direction will be offset by active
transport in the opposite direction. The end result for all ions is no net movement of
charge across the membrane and a stable, resting Vm.
The deflection of Vm from rest is the basis of bioelectrical signal generation. This is
accomplished by changing membrane conductance to an ion (or ions) that is (are)
out of electrochemical equilibrium, resulting in a net membrane current and,
therefore, a change in Vm. The membrane conductance for specific ions is altered
by opening or closing specific “gated” ion channels. A change in membrane
conductance for any ion X, which is not in electrochemical equilibrium, will cause a
change in Ix
Ix =gx(Vm - Ex)
Thus the balance between active and passive fluxes will be transiently disrupted, a
net movement of charge across be transiently disrupted, a net movement of charge
across the membrane will occur, Vm will deflect from its resting value, and a
bioelectrical signal will be generated. For any given change in g, the direction of
the resulting change in 1x and its magnitude, i.e., the nature of the signal, will be
determined by the direction and magnitude of the electrochemical driving force
acting on X.
FIG. 1. A: example of a neuron where electrical and chemical driving forces (EDF
and CDF, respectively) acting on cation X are equal and in opposite directions,
resulting in no net, or electrochemical, driving force (DF) for X, i.e., electrochemical
equilibrium with respect to X. B: example of a neuron where outward CDF for
cation X exceeds inward EDF, resulting in outward net driving force acting on X.
Vm, membrane potential; [x+]i, [x+]e,, intra- and extracellular concentrations of
cation X, respectively.
g: mS/cm2
I: mA/cm2
Vm: -40
EK: -58
Ena: +50
Delta: 18 mV
Delta: -110