The nitroso-donor S-nitroso-cysteine regulates IsK expressed in Xenopus oocytes via a c-GMP independent mechanism.
In Xenopus oocytes expressing slowly activating IsK channels superfusion with the nitroso-donor S-Nitroso-Cysteine (SNOC) resulted in an increase of IsK, which was greatly enhanced when the amino acid-exchanger rBAT was coexpressed. The effects of SNOC on IsK could not be prevented by the guanylate cyclase inhibitor LY-83,583 and the cGMP kinase inhibitor H8, but was abolished in the presence of staurosporine. SNOC also increased the currents induced by the expression of protein mutants lacking intracellular sites, previously described to be involved in IsK regulation by oxidation and phosphorylation. These data suggest that the NO-donor SNOC regulates IsK indirectly via a cGMP independent, but staurosporine sensitive, pathway.
Institute of Physiology, Eberhard-Karls-Universität Tübingen, Germany.
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Raber
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Waldegger
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Herzer
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Gulbins
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Murer
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Busch
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Lang
D000470:Alkaloids / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009603:Nitroso Compounds / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D026403:S-Nitrosothiols; D019311:Staurosporine; D014982:Xenopus laevis
D000470:Alkaloids; D000634:Aminoquinolines; D007546:Isoquinolines; D009603:Nitroso Compounds; D015221:Potassium Channels; D026403:S-Nitrosothiols; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; C041715:6-anilino-5,8-quinolinedione; C021315:S-nitrosocysteine; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019311:Staurosporine; D003545:Cysteine