It is important to stress once more that the transmembrane potential differences we have discussed to this point do not arise directly from the (Na+-K+) pump but indirectly from the ionic asymmetries that are generated by this pump. It is now clearly established, however, that under most circumstances, the (Na+-K+) pump is not neutral (i.e., one to one) but actually extrudes three Na+ from the cell in exchange for two K+. Thus, the pump itself brings about the movement of charge across the membrane (i.e., one positive charge from inside to outside for every cycle) and can be viewed as a current generator. Clearly, inasmuch as the pump generates a current across a membrane with a resistance, its action must directly result in an electrical potential difference given by the product of the pump current and the membrane resistance.
Thus, in general, transmembrane electrical potential differences have two origins. By far the largest fraction of these potential differences is attributable to diffusion potentials due to ionic asymmetries established by (Na+-K+) pumps. But, definite contributions to these potential differences arise directly from the current generated by the (Na+-K+) pump.
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