This study examined the transduction pathways activated by epinepherine in the pacemaker region of the toad heart. Recordings of membrane potential, force, and intracellular Ca2+ concentration ([Ca2+]i) were made from arrested toad sinus venosus. Sympathetic nerve stimulation activated non-α-, non-β-adrenoceptors to evoke a membrane depolarization and a transient increase in [Ca2+]i. In contrast, the β-adrenoceptor agonist isoprenaline (10 μM) caused membrane hyperpolarization and decreased [Ca2+]i. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM) mimicked the isoprenaline-evoked membrane hyperpolarization. Epinephrine (10–50 μM) caused an initial membrane depolarization and an increase in [Ca2+]i followed by membrane hyperpolarization and decreased [Ca2+]i. The membrane depolarizations evoked by sympathetic nerve stimulation or epinephrine were abolished either by the phospholipase C inhibitor U-73122 (20 μM) or by the blocker ofd- myo-inositol 1,4,5,-trisphosphate-induced Ca2+ release, 2-aminoethoxydiphenyl borate (2-APB, 60 μM). Neither U-73122 nor 2-APB had an affect on the membrane hyperpolarization evoked by β-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.
Sympathetic nerve stimulation and applied transmitters on the sinus venosus of the toad.