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 thetransport 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 iscritical 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).1 How, then, does this electrical gradient arise? It is the consequence of the influence oftwo 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 processdevelops 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 theplasma 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 forgeneration 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 acrossit. 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 interactionbetween 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...