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 Ca(2+)-activated K+ current (IKCa2+). 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 IKCa2+ is activated at potentials more positive than -30 mV. Bath application of S-nitroso-L-cysteine increased IKCa2+ by 50% above control levels throughout the entire activation range of potentials. The enhanced current was reversible on washout. Either charybdotoxin, an inhibitor of IKCa2+, or (R)-p-8-(4-chloropenylthio)-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 IKCa2+ via the guanosine 3',5'-cyclic monophosphate-protein kinase G signal transduction pathway.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D009893:Opossums; D011188:Potassium / Q000502:physiology*; D026403:S-Nitrosothiols; D013873:Thionucleotides / Q000494:pharmacology
D026403:S-Nitrosothiols; D013873:Thionucleotides; D018999:Charybdotoxin; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; C021315:S-nitrosocysteine; D006152:Cyclic GMP; D003545:Cysteine; D011188:Potassium; D002118:Calcium