Voltage Sensitivity of the Na+/K+ Pump: Structural Implications
It is now firmly established that the Na+/K+ pump in its normal forward mode exports three sodium ions and imports two potassium ions per cycle (13,22,25). The enzyme thus produces a transmembrane electric current as it hydrolyzes ATP and must, like any chemical battery, for thermodynamic reasons be sensitive to the voltage difference across the cell membrane. For a given Na+:K+:ATP stoichiometry and known conditions (ion gradients; free energy of ATP hydrolysis) only the equilibrium (zero-current or “reversal”) potential can be computed (6). In typical animal cells the reversal potential is expected to be quite negative (≤ -200 mV), i.e. probably beyond experimental reach (4). The shape of the steady-state current-voltage relationship (I-V curve) away from the reversal potential is determined by the kinetic properties of the pump, in particular by the voltage sensitivity of individual steps in the pump’s reaction cycle. Were every step and its voltage sensitivity known, the I-V curve could be deduced from first principles. While such detailed knowledge is lacking, several researchers have examined the predictions of more or less elaborate models. The most comprehensive of these (e.g. 17,18) incorporate possible voltage sensitivity of ion binding, ion translocation, and protein conformational steps. We review here the converse problem: given an experimental voltage dependence curve, what information can be extracted regarding the kinetics of various steps in the pump cycle? Several groups including ours have exploited the pump’s voltage sensitivity to discover during which step(s) a charge is moved across an electric field, or a field is moved across a charge (17).
KeywordsHydrolysis Stein Noma Alan
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