Low concentrations of ouabain stimulate Na/Ca exchange in neurons.

1. The effects of low concentrations of ouabain on 22Na efflux, 86Rb influx, 45Ca uptake and cyclic AMP levels were studied in snail ganglia. Ouabain, at concentrations below that which inhibits the Na-K pump as monitored by 86Rb influx, activated "reverse mode" Na/Ca exchange, as indicated by an increased 22Na efflux and 45Ca influx. 2. With electrophysiologic recordings ouabain, in the presence of K(+)-free saline to block Na/K transport, caused a membrane hyperpolarization. These concentrations of ouabain also caused elevation of intracellular cyclic AMP levels. 3. We suggest that the ouabain-induced stimulation of Na efflux is due to a stimulation of reverse Na/Ca exchange. since Na/Ca exchange is electrogenic, these observations are most consistent with ouabain stimulation of Na/Ca exchange in a reversed direction (intracellular Na for extracellular Ca). 4. The effect on Na/Ca exchange may be secondary to a rise in intracellular cyclic AMP.