Voltage dependence of Na translocation by the Na/K pump

Abstract

During each complete reaction cycle, the Na/K pump transports three Na ions out across the cell membrane and two K ions in. The resulting net extrusion of positive charge generates outward membrane current but, until now, it was unclear how that net charge movement occurs. Reasonable possibilities included a single positive charge moving outwards during Na translocation; or a single negative charge moving inwards during K translocation; or either positive or negative charges moving during both translocation steps, but in unequal quantities. Any step that involves net charge movement through the membrane must have voltage-dependent transition rates. Here we report measurements of transient, voltage-dependent, displacement currents generated by the pump when its normal Na/K transport cycle has been interrupted by removal of external K and it is thus constrained to carry out Na/Na exchange. The quantity and voltage sensitivity of the charge moved during these transient currents suggests that Na translocation includes a voltage-dependent transition involving movement of one positive charge across the membrane. This single step can thus fully account for the electrogenic nature of Na/K exchange. The result provides important new insight into the molecular mechanism of active cation transport.