Na+-Ca2+ exchange is affected by membrane potential in cardiac sarcolemmal vesicles

The effect of membrane potential on the Na+-Ca2+ exchange activity of isolated sarcolemmal vesicles from dog ventricles is examined. Na+-Ca2+ exchange is monitored as Nai+-dependent Ca2+ uptake as described by Reeves and Sutko ((1979) Proc. Natl. Acad. Sci. U. S. A. 76,590-594). Membrane potential is controlled by varying internal and external K+ in the presence of valinomycin. Inside-positive potentials stimulate Nai+-dependent Ca2+ influx. This stimulation is independent of Ca2+ concentration. The results indicate that Na+-Ca2+ exchange by itself can generate a substantial potential (approximately -60mV) in the sarcolemmal vesicles. The data are consistent with an electrogenic Na+-Ca2+ exchange mechanism in which three or more Na+ are exchanged for one Ca2+. This electrogenic exchange may have important implications in the control of myocardial tension development.