Parallel metabotropic pathways in the heart of the toad, Bufo marinus

This study examined the transduction pathways activated by epinepherine in the pacemaker region of the toad heart. Recordings of membrane potential, f orce, and intracellular Ca2+ concentration ([Ca2+](i)) were made from arres ted toad sinus venosus. Sympathetic nerve stimulation activated non-alpha-, non-beta -adrenoceptors to evoke a membrane depolarization and a transient increase in [Ca2+](i). In contrast, the beta -adrenoceptor agonist isopren aline (10 muM) caused membrane hyperpolarization. and decreased [Ca2+](i). The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM) mimick ed the isoprenaline-evoked membrane hyperpolarization. Epinephrine (10-50 m uM) caused an initial membrane depolarization and an increase in [Ca2+](i) followed by membrane hyperpolarization and decreased [Ca2+](i). The membran e depolarizations evoked by sympathetic nerve stimulation or epinephrine we re abolished either by the phospholipase C inhibitor U-73122 (20 muM) or by the blocker of D-myo-inositol 1,4,5,-trisphosphate-induced Ca2+ release, 2 -aminoethoxydiphenyl borate (2-APB, 60 muM). Neither U-73122 nor 2-APB had an affect on the membrane hyperpolarization evoked by beta -adrenoceptor ac tivation. These results suggest that in the toad sinus venosus, two distinc t transduction pathways can be activated by epinephrine to cause an increas e in heart rate.