Modulation of calcium channel expression in cardiac myocytes of rats during growth hormone-induced growth or normal postnatal development

Abstract

Voltage-dependent Ca$\sp{2+}$ currents of cardiac myocytes were studied using patch-clamp techniques. T-type Ca$\sp{2+}$ current density of atrial myocytes was found to be positively correlated with the plasma growth hormone levels and the growth rate of atrial myocytes in normally developing Sprague-Dawley rats, adult Wistar-Furth rats made to reenter an active growth phase following implantation of a growth hormone-secreting tumor, and mutant dwarf rats with retarded growth due to a specific deficiency in pituitary growth hormone synthesis. The voltage and time dependent activation and inactivation of T-type Ca$\sp{2+}$ current are not changed in spite of the changes in T-current density. The unchanged macroscopic current properties and constant single T-channel current suggest that the change in T-current density is likely due to a change in membrane density of T-type Ca$\sp{2+}$ channels rather than a change in the channel protein itself. Though atrial T-current density increases when plasma growth hormone levels are high, it is difficult to prove the involvement of growth hormone in regulating Ca$\sp{2+}$ channel expression because of the complication from other hormones and growth factors. It is also possible that the correlation between atrial T-current density and plasma growth hormone levels is merely accidental. The up-regulation of T-type Ca$\sp{2+}$ channel density during active growth is specific for atrial myocytes, since T-type Ca$\sp{2+}$ current is not induced in ventricular myocytes from the tumor-bearing rats. High T-current density during the period of active growth of atrial myocytes supports the idea that T-type Ca$\sp{2+}$ channels may have some role in embryonic/postnatal development in certain tissues. L-type Ca$\sp{2+}$ channels are regulated in a different way. In contrast to T-type Ca$\sp{2+}$ current, L-type Ca$\sp{2+}$ current density remains constant in both atrial and ventricular cells from rats during either normal postnatal development in young rats or induced active growth in adult rats bearing growth hormone-secreting tumors. The constant L-current density may be important to keep up Ca$\sp{2+}$ influx with increased cell size to support normal cardiac contraction.