title: Inhibition of human IsK channels expressed in Xenopus oocytes by calmodulin antagonists.
abstract: The calmodulin antagonists, trifluoperazine, chlorpromazine and W7 (10-[3-(4-methyl-1-piperazinyl)-propyl]-2-(trifluomethyl)-10H-phen othiazine , 2-chloro-10-(dimethylaminopropyl)-phenothiazine and N-(6-aminohexyl)-5-chloro-1-naphtalen-sulfonamide, respectively), were tested for their effects on human IsK channels expressed in Xenopus oocytes and their interference with the previously described [Ca2+]i-mediated regulation of IsK. An increase in [Ca2+]i accelerated IsK activation and increased the current amplitude, as has been previously observed. Chlorpromazine, trifluoperazine and W7 inhibited depolarization-activated IsK channels with an EC50 between 70 and 100 microM. None of the calmodulin antagonists abolished the regulation of IsK by A23187 (calcimycin) or hypotonic extracellular fluid, although the inhibitory effects of these compounds were also obvious after enhancement of [Ca2+]i. In conclusion, the calmodulin antagonists inhibit IsK at both physiological and enhanced [Ca2+]i.
authors.affiliation: Physiologisches Institut I, Eberhard-Karls-Universität Tübingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Herzer
authors.forename: A E
authors.initials: AE
authors.lastname: Busch
authors.forename: S
authors.initials: S
authors.lastname: Waldegger
authors.forename: F
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D007038:Hypotonic Solutions / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D018075:RNA, Complementary / Q000096:biosynthesis; D014982:Xenopus laevis
chemical_list: D002147:Calmodulin; D007038:Hypotonic Solutions; D015221:Potassium Channels; D018075:RNA, Complementary; D000001:Calcimycin