Na+/Ca2+ EXCHANGE is electrogenic and moves one net positive charge per cycle1,2. Although the cardiac exchanger has a three-to-one Na+/Ca2+ stoichiometry3, details of the reaction cycle are not well defined2,4-8. Here we associate Na+ translocation by the cardiac exchanger with positive charge movement in giant membrane patches from cardiac myocytes9,10 and oocytes expressing the cloned cardiac Na+/Ca2+ exchanger11. The charge movements are initiated by step increments of the cytoplasmic Na+ concentration in the absence of Ca2+. Giant patches from control oocytes lack both steady-state Na+/Ca2+ exchange current (INaCa) Na+-induced charge movements. Charge movements indicate about 400 exchangers per (μm2 in guinea-pig sarcolemma. Fully activated INaCa densities (20-30 μA cm-2) indicate maximum turnover rates of 5,000s-1. As has been predicted for consecutive exchange models4-7, the apparent ion affinities of steady stateINaCa increase as the counterion concentrations are decreased. Consistent with an electroneutral Ca2+ translocation, we find that voltage dependence of INaCa in both directions is lost as Ca2+ concentration is decreased. The principal electrogenic step seems to be at the extracellular end of the Na+ translocation pathway.
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