Dexamethasone-induced hypertrophy in rat neonatal cardiac myocytes involves an elevated L-type Ca2+ current

The mechanism responsible for dexamethasone-induced hypertrophy in infants has not been defined. In this study, we have investigated the role of L-typ e Ca2+ currents in the development of dexamethasone-induced hypertrophy in rat neonatal cardiac myocytes. Using cytoplasmic membrane capacitance measu rements, we have shown that the size of the cells treated with dexamethason e were larger than those of the control cells. In addition, treating the ce lls with 1 mu M dexamethasone for 48 h increased L-type Ca2+ current densit y significantly, without affecting the voltage-dependent activation and ste ady state inactivation of the current. The increase in current density was associated with an elevation of the mRNA transcript encoding the L-type Ca2 + channel subunit alpha(1)C. Dexamethasone treatment also resulted in an in crease in the peak amplitude of the intracellular Ca2+ transient measured b y fura-2/epifluorescence. Finally, we have demonstrated that the hypertroph ic effect of dexamethasone, characterized by the ratio of protein content p er cell, was blocked by the L-type specific antagonist, nifedipine. In conc lusion, an elevation of L-type Ca2+ current is involved in the process of d examethasone-induced cardiac myocyte hypertrophy in neonatal rats. (C) 1999 Academic Press.