Spontaneous activity of sodium loaded guinea-pig cardiac myocytes: contribution of Na+/Ca2+ exchange.

Guinea-pig cardiac myocytes loaded intracellularly with Na+ show spontaneous contractile activity and transient membrane depolarizations or inward currents. We have investigated whether both phenomena can be attributed to release of Ca2+ from overloaded cellular stores causing contractile activation and at the same time generating an inward current due to Ca2+ efflux by the electrogenic Na+/Ca2+ exchange. Variations in membrane potential by voltage clamp or in ionic composition of the superfusion medium changed the amplitude and frequency of spontaneous inward currents in the direction expected from computations of the Na+/Ca2+ exchange. Caffeine in concentrations that activate the Ca2+ release channel of the sarcoplasmic reticulum produced a vigorous contraction accompanied by a large current transient. After exposure to ryanodine both Isp and spontaneous contractions were abolished. Spontaneous inward currents were depressed by inhibitors of the Na+/Ca2+ exchange. The results with caffeine and ryanodine demonstrate that unimpaired sarcoplasmic reticular function is a prerequisite for both the contractile and the electrical event. From the characteristics of Isp it is proposed that this current is due to electrogenic Na+/Ca2+ exchange.