Developmental changes in beta-adrenergic and muscarinic modulations of Ca2+ currents in fetal and neonatal ventricular cardiomyocytes of the rat

Abstract

Developmental changes of the beta-adrenergic and muscarinic modulations acting on the slow Ca2+ channels in rat ventricular cardiomyocytes were investigated using Ba2+ as the charge carrier (IBa(L)). Single cardiomyocytes from fetal and neonatal rats were freshly isolated, and currents were recorded by whole-cell voltage clamp in Na(+)-free, K(+)-free external solution. Basal current densities showed a large increase between fetal days 15 and 18, and a small decrease after fetal day 20. The ability of isoproterenol (ISO, 1 microM) to enhance IBa(L) increased dramatically between fetal days 18 and 20, and remained almost constant thereafter during the neonatal period. The ability of forskolin (FOR, 10 microM) to stimulate IBa(L) also increased markedly between fetal day 18 and neonatal day 1. Carbachol (CCh), in a dose-dependent manner, reversed the stimulation of the IBa(L) produced by ISO in neonatal cardiomyocytes. The IC50 values for CCh inhibition of IBa(L) was almost the same on all neonatal days tested (neonatal days 1, 5 and 10). The results indicate that there are developmental changes in beta-adrenergic modulation of IBa(L) in the late fetal period, including a large jump in sensitivity to ISO on about fetal day 19. These findings are consistent with the steep increase in number of beta-adrenergic receptors that occurs between fetal days 18 and 20 (Kojima, Sperelakis & Sada, 1990a: Kojima, Ishima, Taniguchi, Kimura, Sada & Sperelakis, 1990C).