Voltage dependence of the Na/K pump.

Present evidence demonstrates that the Na-K pump rate is voltage dependent, whereas early work was largely inconclusive. The I-V relationship has a positive slope over a wide voltage range, and the existence of a negative slope region is now doubtful. Monotonic voltage dependence is consistent with the reaction cycle containing a single voltage-dependent step. Recent measurements suggest that this voltage-dependent step occurs during Na translocation and may be deocclusion of Na+. In addition, two results suggest that K translocation is voltage insensitive: (a) large positive potentials appear to have no influence on Rb-Rb exchange or associated conformational transitions; and (b) transient currents associated with Na translocation appear to involve movement of a single charge, which is sufficient for a 3Na-2K cycle. The simplest interpretation is that the pump's cation binding sites supply two negative charges. Pre-steady-state measurements demonstrate that Na translocation precedes the pump cycle's rate-limiting step, presumably K translocation. But, because K translocation seems voltage insensitive, the voltage dependence of the steady-state pump rate probably reflects that of the concentration of the intermediate entering this slow step. Further pump current and flux data (both transient and steady-state), carefully determined over a range of conditions, should increase our understanding of the voltage-dependent step(s) in the Na-K pump cycle.