ELECTROGENIC ION PUMPS

Some years ago I was partly responsible for unearthing the first experimental evidence', on the coupling of the outward movement of sodium and the inward movement of potassium in nerve and muscle fibers. So far as the detailed mechanism of ion pumping is concerned, this early work could be said to have put us somewhat off the scent, by suggesting that the process normally involves a fairly tight coupling between the fluxes of different ions as they cross the membrane in opposite directions, although Hodgkin and I2 were in fact careful to point out that the linkage between sodium and potassium was unlikely to be obligatory. Since then, it has become clear that 1 : 1 coupling may be the exception rather than the rule, and although it must apply to the net fluxes in cells such as erythrocytes, in which the influx of potassium always takes place against a large electrochemical gradient, there is now plenty of evidence (derived principally from studies of excitable tissues 3, of the operation of electrogenic pumps that extrude sodium ions and at the same time create an electric potential difference across the membrane. In diagrammatic terms (FIGURE l ) , there is no difficulty in envisaging a mechanism in which the degree of coupling is variable, and we have shown that in frog muscle the tightness of the linkage must be regarded as depending on several factors, of which the internal sodium and the external potassium concentrations are possibly the most important. If the unidirectional fluxes of labeled ions are considered, rather than the net fluxes, the picture of course becomes still more complicated, because of the occurrence of sodium-sodium exchange fluxes, the magnitude of which varies with the level of ATP supplied to the pump 5 , (and doubtless with other factors as well). The lesson to be derived from all this by students of mitochondria1 function is that the sodium pump provides a good precedent, if one is needed, for the proposal that an active transport system may exist for ions, and that it can be electrically neutral in its operation, or electrogenic, or somewhere in between, depending on the conditions that prevail. It would be a grave mistake, however, to suppose that the sodium pump is the only type of electrogenic ion pump known to cell physiologists, or even that it is the best model of ionic transport in mitochondria and other subcellular organelles. It may be the most ubiquitous, and certainly (thanks to the availability in cardiac glycosides such as ouabain of highly specific blocking agents) it is the most intensively studied active transport mechanism. But we know of several other ionic transport systems the properties of which may actually be more relevant to today's discussion than are those of the sodium pump.i In the excretory organs of insects, for example, there is a potassium pump capable of prodigies of ion transport, which is quite certainly not to be identified with Na,K-ATPase, if only because it is not affected by ouabain and indeed shows no detectable ATPase activity.$ There are certain other features of this system, which is Pump V in my classification,i*S that seem