Alpha-adrenoceptor stimulation induces hypertrophy and increases L-type calcium current density in neonatal rat ventricular cardiomyocytes in culture.

Effects of chronic alpha-adrenoceptor stimulation on hypertrophy and L-type calcium current (I(Ca-L) ) were investigated in neonatal rat ventricular cardiomyocytes in culture using whole-cell patch-clamp technique and measurement of protein- and RNA-to-DNA ratios. Chronic exposure to norepinephrine (2 microM) plus propranolol (2 microM) of cardiomyocytes during 1 and 3 days in culture increased cell membrane capacitance, protein- and RNA-to DNA ratios and was accompanied by an increase in I(Ca-L) density. These effects were not observed in the presence of prazosin (2 microM) suggesting that they could be due to alpha(1) -adrenoceptor stimulation. They were also prevented by cycloheximide (5 microM) and actinomycin D (1 microM). These effects were not observed in 1 and 3 day-cultured cells pre-treated for only 1 hour with norepinephrine. They were potentiated when calcium concentration was increased in the culture medium and, in contrast they were abolished in the presence of the L-type calcium current inhibitor, nifedipine (2 microM). The present study demonstrates that hypertrophy induced by long-term stimulation of alpha(1) -adrenoceptors is accompanied by an increase in the expression of functional calcium channels in neonatal rat cardiomyocytes. These results reveal the existence of a novel alpha(1) -mediated positive regulation of L-type calcium current different from that due to acute stimulation of alpha(1) -adrenoceptors in neonatal ventricular cardiomyocytes.