The effects of endothelin-1 on the PKA-dependent Cl- current in the heart.
The effects of endothelin-1 (ET-1) on whole-cell cardiac PKA-dependent Cl- currents (ICl) were investigated using patch clamp techniques. ET-1 inhibited the isoproterenol-induced ICl with a half-maximally effective concentration of approximately 1 nM. ET-1 also inhibited the forskolin-induced current in a similar concentration range. The effects of ET-1 were abolished by pre-treatment of the cells with pertussis toxin. Since ET-1 was ineffective at inhibiting the ICl induced by internal dialysis with cyclic AMP, it is unlikely that the Gi-protein had a direct effect on channel gating or phosphorylation of the channel by PKA. It is concluded that ET-1 inhibited the cardiac PKA-dependent ICl by attenuating activation of adenylate cyclase and that this effect was mediated by a pertussis toxin-sensitive G-protein, presumably Gi.
James
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AF
International Research Laboratories, Ciba-Geigy Japan Ltd., Takarazuka, Japan.
Xie
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LH
Horie
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D037361:Adenylate Cyclase Toxin; D000818:Animals; D018118:Chloride Channels / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000633:toxicity
D037361:Adenylate Cyclase Toxin; D018118:Chloride Channels; D016232:Endothelins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol