title: Parallel metabotropic pathways in the heart of the toad, Bufo marinus.
abstract: This study examined the transduction pathways activated by epinephrine in the pacemaker region of the toad heart. Recordings of membrane potential, force, and intracellular Ca(2+) concentration ([Ca(2+)](i)) were made from arrested toad sinus venosus. Sympathetic nerve stimulation activated non-alpha-, non-beta-adrenoceptors to evoke a membrane depolarization and a transient increase in [Ca(2+)](i). In contrast, the beta-adrenoceptor agonist isoprenaline (10 microM) caused membrane hyperpolarization and decreased [Ca(2+)](i). The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM) mimicked the isoprenaline-evoked membrane hyperpolarization. Epinephrine (10-50 microM) caused an initial membrane depolarization and an increase in [Ca(2+)](i) followed by membrane hyperpolarization and decreased [Ca(2+)](i). The membrane depolarizations evoked by sympathetic nerve stimulation or epinephrine were abolished either by the phospholipase C inhibitor U-73122 (20 microM) or by the blocker of D-myo-inositol 1,4,5,-trisphosphate-induced Ca(2+) release, 2-aminoethoxydiphenyl borate (2-APB, 60 microM). Neither U-73122 nor 2-APB had an affect on the membrane hyperpolarization evoked by beta-adrenoceptor activation. These results suggest that in the toad sinus venosus, two distinct transduction pathways can be activated by epinephrine to cause an increase in heart rate.
authors.affiliation: Department of Zoology, University of Melbourne, Victoria, Australia 3010. narelleb@unimelb.edu.au
authors.forename: N J
authors.initials: NJ
authors.lastname: Bramich
authors.forename: H M
authors.initials: HM
authors.lastname: Cousins
authors.forename: F R
authors.initials: FR
authors.lastname: Edwards
authors.forename: G D
authors.initials: GD
authors.lastname: Hirst
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D002024:Bufo marinus; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006324:Heart Arrest, Induced; D006329:Heart Conduction System / Q000503:physiopathology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D000322:Adrenergic Agonists; D002316:Cardiotonic Agents; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D010738:Type C Phospholipases; D007545:Isoproterenol; D002118:Calcium; D004837:Epinephrine