Little information is available concerning the modulation of cardiac function by -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 µM) 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 (I_Ba). In 9.5-dpc myocytes, I_Ba 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 µM) reversed the effect of Iso. Forskolin (For, 10 µM) produced an increase in I_Ba by 95.5 ± 18.8% (n = 8). In ventricular myocytes at a late embryonic stage (18 dpc), 3 µM Iso caused an appreciably greater increase in I_Ba from 6.2 ± 0.5 to 14.5 ± 2.2 pA/pF (by 137.8 ± 33.0%, n = 8), whereas the increase in I_Ba by 10 µM 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 -adrenergic receptors in the embryonic mouse heart as early as 9.5 dpc, probably via a cAMP-dependent pathway.

calcium ion channels; -adrenergic receptor; isoproterenol

This article has been cited by other articles:

				N. Niwa, K. Yasui, T. Opthof, H. Takemura, A. Shimizu, M. Horiba, J.-K. Lee, H. Honjo, K. Kamiya, and I. Kodama Cav3.2 subunit underlies the functional T-type Ca2+ channel in murine hearts during the embryonic period Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2257 - H2263. [Abstract] [Full Text] [PDF]

				K. Banach, M. D. Halbach, P. Hu, J. Hescheler, and U. Egert Development of electrical activity in cardiac myocyte aggregates derived from mouse embryonic stem cells Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2114 - H2123. [Abstract] [Full Text] [PDF]

				G. A. Porter Jr. and S. A. Rivkees Ontogeny of humoral heart rate regulation in the embryonic mouse Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2001; 281(2): R401 - R407. [Abstract] [Full Text] [PDF]

				K. Yasui, W. Liu, T. Opthof, K. Kada, J.-K. Lee, K. Kamiya, and I. Kodama If Current and Spontaneous Activity in Mouse Embryonic Ventricular Myocytes Circ. Res., March 16, 2001; 88(5): 536 - 542. [Abstract] [Full Text] [PDF]