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.
Pignier
C
C
Laboratoire de Physiologie Générale, CNRS UMR 6558; 86022 Poitiers cedex, France.
Levan-Petit
I
I
Ancey
C
C
Potreau
D
D
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology*; D006984:Hypertrophy; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D020746:Calcium Channels, L-Type; D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D009638:Norepinephrine