Potassium current inhibition by nonselective cation channel-mediated sodium entry in rat pheochromocytoma (PC-12) cells

Under physiological conditions, nonselective cation (NSC) channels mediate the entry of cations into cells, the most important being Na+ and Ca2+. In contrast to the Ca(2+)-dependent signaling mechanisms, little is known about the consequences and the spatial distribution of intracellular [Na+] elevation. In this study we demonstrate that Na+ entry, during the opening of ATP-activated NSC channels, leads to an inhibition of voltage-dependent K+ currents (IK) in cromaffin-like undifferentiated PC-12 cells. The effect was dependent on the charge carrier as well as on the density of the ATP-activated current. Extracellular alkali cations (Na+, Li+) were more efficient than NH4+ in suppressing IK. Intracellular infusion of Na+ had the same effect as Na+ influx through ATP-activated NSC channels. The inhibition of IK persisted when the total ATP-induced Na+ entry was reduced by membrane depolarization, suggesting a spatial restriction of the required Na+ accumulation. Our results indicate that NSC channels influence the function of other ion channels by changing local intracellular ion concentrations.