title: Autonomic regulation of cardiac chloride current.
abstract: The cellular mechanism of autonomic regulation of the catecholamine-induced chloride current (ICl) was investigated by recording the whole-cell current in isolated guinea-pig ventricular cells. The beta-adrenergic and related stimulations such as adrenaline, isoprenaline, forskolin, or internal application of cyclic AMP (cAMP), induced the ICl. Acetylcholine (ACh) depressed the responses of ICl induced by the beta-adrenergic stimulation or forskolin, which was followed by a transient overshoot of the ICl response upon washing out ACh. ACh failed to interfere with ICl induced by cAMP, and the pretreatment of myocytes with pertussis toxin (PTX) abolished the inhibitory effect of acetylcholine. Intracellular application of cGMP, which levels are known to be elevated by the muscarinic stimulation, enhanced ICl activated by submaximal doses of isoprenaline. In the absence of agonists, cGMP failed to induce ICl. Thus, the antagonistic interaction between the beta-adrenergic stimulation and the muscarinic stimulation is at the membrane level, most probably via PTX-sensitive GTP-binding proteins. cGMP might contribute to the post-ACh rebound phenomenon by facilitating the beta-stimulation.
authors.affiliation: Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: A
authors.initials: A
authors.lastname: Noma
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology*; D018118:Chloride Channels / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology
chemical_list: D001337:Autonomic Agents; D018118:Chloride Channels; D005576:Colforsin; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D000109:Acetylcholine; D015056:1-Methyl-3-isobutylxanthine