POTASSIUM CURRENT INHIBITION BY NONSELECTIVE CATION CHANNEL-MEDIATED SODIUM ENTRY IN RAT PHEOCHROMOCYTOMA (PC-12) CELLS

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