Parallel metabotropic pathways in the heart of the toad, Bufo marinus.
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.
Bramich
N J
NJ
Department of Zoology, University of Melbourne, Victoria, Australia 3010. narelleb@unimelb.edu.au
Cousins
H M
HM
Edwards
F R
FR
Hirst
G D
GD
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
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