The Na-K pump as a current source. Affinity-driven transport has no reversal potential but its metabolic cost does

Dear Sir: In an earlier letter on another matter, Chapman and Johnson (1978) identified a paradox facing a widely held stoichiometric model for ATP utilization in active ion transport. Their well-reasoned and carefully documented argument summarized two apparently conflicting points of evidence. First, the net rate of ATP hydrolysis not only varies with imposed brief displacements of the transmembrane electric potential difference, but ceases at, and reverses direction to net synthesis beyond, a reversal potential that may not be far from the cell's resting potential. Second, the active transport fluxes of sodium and potassium remain essentially constant over this same range of transmembrane potentials. According to the stoichiometric concept in question, the net hydrolysis of one ATP molecule drives a stoichiometrically fixed number of ions of each actively transported species in a specific direction through the cell membrane. One then expects the net ATP turnover rate' and the active transport rates to remain strictly proportional, or tightly coupled, during displacements of the membrane potential, and that all should go to zero simultaneously at the reversal potential for net ATP hydrolysis. The evidence just cited is therefore paradoxical for this net-turnover stoichiometric (NTS) model. Chapman and Johnson argued that this difficulty can be resolved in a way that preserves the overall stoichiometry, as well as essentially voltage-independent pump fluxes over much of the physiological range, provided certain kinetic relationships obtain among fluxes, ATP turnover, substrate concentrations , and membrane potential (see also Chapman et al., 1979; Chapman, 1981). Moreover, they suggested new experiments to test for simultaneous reversal of active pump fluxes and net ATP turnover. But they also cautioned that unless simultaneous reversal can be demonstrated experimentally, a major rethinking of the pump's mechanism and stoichiometry may be in order. The purpose of this letter is to point out that Kedem's (1961) concept of ' I use "hydrolysis rate," "turnover," and "turnover rate" interchangeably in this discussion .