beta-adrenergic modulation of L-type Ca2+-channel currents in early-stage embryonic mouse heart

Little information is available concerning the modulation of cardiac function by beta-adrenergic agonists in early-stage embryonic mammalian heart. We have examined the effects of isoproterenol (Iso) on the spontaneous beating rate and action potential (AP) configuration in embryonic mouse hearts at 9.5 days postcoitum (dpc), just 1 day after they started to beat. Iso (3 microM) increased the spontaneous beating rate in whole hearts, dissected ventricles, and isolated ventricular myocytes. In ventricular myocytes, Iso also increased the slope of the pacemaker potential and the action potential duration but decreased the maximum upstroke velocity. In whole cell voltage-clamp experiments, the Ca2+-channel currents were measured as Ba2+ currents (IBa). In 9.5-dpc myocytes, IBa was enhanced significantly from -4.7 +/- 0.9 to -6.7 +/- 1.2 pA/pF (by 52.4 +/- 14.8%, n = 10) after the application of Iso. Propranolol (3 microM) reversed the effect of Iso. Forskolin (For, 10 microM) produced an increase in IBa by 95.5 +/- 18.8% (n = 8). In ventricular myocytes at a late embryonic stage (18 dpc), 3 microM Iso caused an appreciably greater increase in IBa from -6.2 +/- 0.5 to -14.5 +/- 2.2 pA/pF (by 137.8 +/- 33.0%, n = 8), whereas the increase in IBa by 10 microM For (by 120.0 +/- 23.0%, n = 7) was comparable to that observed in the early stage (9.5 dpc). These results indicate that the L-type Ca2+-channel currents are modulated by beta-adrenergic receptors in the embryonic mouse heart as early as 9.5 dpc, probably via a cAMP-dependent pathway.