Cell cycle-related changes in the voltage-gated Ca2+ currents in cultured newborn rat ventricular myocytes

The expression of T-type Ca2+ current (I-Ca,I- (T)) has been reported to change during postnatal heart development and myocardial hypertrophy, which are characterized respectively by the arrest of the cell cycle soon after birth and a switching on of DNA synthesis in the terminally differentiated cardiac myocytes. The hypothesis that there are cell cycle-related changes in cardiac Ca2+ channel expression was tested by performing whole-c:ell voltage-clamp recording and Bromodeoxy Uridine (BrdU) immunolabeling to determine the S phase of the cell cycle in the same single cultured newborn rat ventricular cells. Myocytes were isolated from 1-day-old Wistar rats and cultured for 15 days. I-Ca,I- (T) was detected in 27% of the 5-day cultured myocytes, The progressive loss of I-Ca,I- (T) during the period of 15-day incubation, which resembles the developmental changes in vivo, paralleled the decrease in the percentage of cells showing BrdU labeling. At day 5 of cell culture, the fraction of myocytes expressing I-Ca,I- (T) was significantly higher in the BrdU-labeled population (95%) as compared with the non-labeled cells (19%), In addition, a 72-h treatment with 20 mu M nickel, an I-Ca,I- (T) blocker. revealed no effect on the percentage of BrdU-positive cells, L-type Ca2+ current (I-Ca,I- (L)) was constantly expressed throughout the 15-day cell culture. The frequency of I-Ca,I- (L) expression was identical between the BrdU-labeled and the non-labeled myocytes, although the latter cell population demonstrated a relatively greater current density. No differences in the inactivating kinetics of I-Ca,I- (L) and their reaction to beta-adrenoceptor stimulation were observed between the two groups. These findings provide convincing evidence for the cell cycle-related expression of cardiac Ca2+ channel. Cardiomyocytes at the S phase of the cell cycle predominantly express I-Ca,I- (T), while the major properties of I-Ca,I- (L) are unchanged during the cell cycle. Such a cell cycle-related channel expression may play a critical role in regulating the cardiac electrophysiological properties during heart development and myocardial remodeling. (C) 1998 Academic Press.