Sodium-calcium exchange activity generates a current in cardiac membrane vesicles.

Sarcolemmal membrane vesicles isolated from canine ventricular tissue accumulate calcium through the sodium-calcium exchange system when an outwardly directed sodium gradient is generated across the vesicle membrane. Moreover, calcium uptake under these conditions is accompanied by the transient accumulation of the lipophilic cation tetraphenylphosphonium. Since the distribution of tetraphenylphosphonium across biological membranes reflects the magnitude and direction of transmembrane potential differences and the characteristics of the transient accumulation of this cation closely resemble those of sodium-calcium exchange activity, it is concluded that a membrane potential, interior negative, is produced during calcium accumulation through the exchange system. Thus, the operation of the sodium-calcium exchange system generates a current in cardiac membrane vesicles, suggesting that three or more sodium ions exchange for each calcium ion.