Contributions of electrogenic pumps to resting membrane potentials: the theory of electrogenic potentials.

Pumped and transported components of ionic flux have been added to passive electrodiffusive components. This permits the derivation of equations for the resting membrane potential that take account of electrogenic mechanisms in which the transport mechanism or pump itself produces a net ionic current. Such equations are general in that they apply to non-steady-state conditions in which intracellular ionic concentrations are changing. The equations developed allow calculation of resting membrane potentials in terms of ionic concentrations, membrane permeability to ions, and kinetic relations for pumped ionic fluxes. When applied to skeletal muscle fibers, the equations predict a buffering effect of the Na/K pump on the membrane potential over a wide range in the values [K]i and [Na]i such that a fairly constant membrane potential occurs under conditions in which the passive ionic fluxes themselves would produce increasing degrees of depolarization. A plot of the membrane potential versus log [K]o with an electrogenic Na pump present gives a curve with slopes both greater than and less than 58 mV per 10-fold concentration change. Over a middle range of [K]o values, the slope is 58 mV. The slope of Em versus log [K]o curves is, therefore, not a very sensitive test for the presence of an electrogenic pump. For the same internal ionic concentrations, less electrogenic increment in membrane potential is observed the higher the value of [K]o, and the more depolarized the membrane. This is due to a rectification present in the pump current-voltage curve, which requires that more pump current be present to produce a given membrane hyperpolarization at depolarized values of the potential than at hyperpolarized values of the potential. A gain in Na and a loss of K by the fibers affects the rectification curve in such a way that less pump current is required to produce the same degree of hyperpolarization. This mechanism ensures that adequate internal negativity will be maintained at high values of [Na]i and [K]o where saturation of the pumping rates might be expected. In the non-steady state of Na extrusion, the condition for which these equations were developed, it is clearly possible for the Na pump to generate potentials considerably higher than those generated under steady-state conditions. For steady-state conditions, both skeletal muscle and squid giant axon Na pumps generate additional internal negativity amounting to a few millivolts.(ABSTRACT TRUNCATED AT 400 WORDS)