Nitric oxide modulates a calcium-activated potassium current in muscle cells from opossum esophagus

Nitric oxide mediates nerve-induced hyperpolarization of circular smooth muscle of the esophagus. Two mechanisms are proposed to explain this hyperpolarization: an increase in K⁺ current or a decrease in Cl current. These studies test the hypothesis that nitric oxide increases a K⁺ current in esophageal smooth muscle. Three outward K⁺ currents are present in circular smooth muscle cells from the opossum esophagus. One current is a Ca²⁺-activated K⁺ current (I(KCa²⁺)). This current is inhibited by charybdotoxin. Whole cell currents were recorded from isolated opossum esophageal smooth muscle cells using the whole cell patch-clamp technique. These studies showed that I(KCa²⁺) is activated at potentials more positive than -30 mV. Bath application of S-nitroso-L-cysteine increased I(KCa²⁺) by 50% above control levels throughout the entire activation range of potentials. The enhanced current was reversible on washout. Either charybdotoxin, an inhibitor of I(KCa²⁺), or (R)-p-8-(4-chlorophenylthio)- guanosine 3',5'-cyclic monophosphorothioate, an inhibitor of protein kinase G, antagonized the increase in outward current induced by S-nitroso-L- cysteine. These data suggest that nitric oxide activates I(KCa²⁺) via the guanosine 3',5'-cyclic monophosphate-protein kinase G signal transduction pathway.