NITRIC-OXIDE MODULATES A CALCIUM-ACTIVATED POTASSIUM CURRENT IN MUSCLE-CELLS FROM OPOSSUM ESOPHAGUS

Nitric oxide mediates nerve-induced hyperpolarization of circular smoo th muscle of the esophagus. Two mechanisms are proposed to explain thi s hyperpolarization: an increase in K+ current or a decrease in Cl- cu rrent. 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. O ne current is a Ca2+- activated K+ current (I-K Ca 2+. This current is inhibited by charybdotoxin. Whole cell currents were recorded from is olated opossum esophageal smooth muscle cells using the whole cell pat ch-clamp technique. These studies showed that I-K Ca 2+ is activated a t potentials more positive than -30 mV. Bath application of S-nitroso- L-cysteine increased I-K Ca 2+ by 50% above control levels throughout the entire activation range of potentials. The enhanced current was re versible on washout. Either charybdotoxin, an inhibitor of I-K Ca 2+, or (R)-p-8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphoroth ioate, an inhibitor of protein kinase G, antagonized the increase in o utward current induced by S-nitroso-L-cysteine. These data suggest tha t nitric oxide activates I-K Ca 2+ via the guanosine 3',5'-cyclic mono phosphate-protein kinase G signal transduction pathway.