Electrophysiological properties of neonatal rat ventricular myocytes with alpha1-adrenergic-induced hypertrophy.
The electrophysiology of neonatal rat ventricular myocytes with and without hypertrophy has not been characterized. The alpha1-adrenergic agonist phenylephrine induced hypertrophy in neonatal rat ventricular myocytes. After 48 h of exposure to 20 microM phenylephrine, cell surface area of hypertrophied myocytes was 44% larger than control. Action potential duration was significantly longer in hypertrophy than in control. There was an increase in L-type Ca2+ current in control after 48 h in culture, but current density was significantly less in hypertrophy (-4.7 +/- 0.8 hypertrophy vs. -10.7 +/- 1.2 control pA/pF, n = 22, P < 0.05). T-type Ca2+ current density was not different. The alpha-adrenergic antagonist prazosin blocked the hypertrophy and the chronic effect of phenylephrine on L-type Ca2+ current. Transient outward K+ current density was decreased 70% in hypertrophy and was blocked with 4-aminopyridine. No change in Na+ current density was observed. Staurosporine, a protein kinase C inhibitor, eliminated the hypertrophy and the effect on L-type Ca2+ current. These studies showed that phenylephrine-induced hypertrophy occurred via the alpha1-adrenergic pathway and caused electrophysiological changes and effects on ion channel expression.
Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
J P
JP
Gaughan
C A
CA
Hefner
S R
SR
Houser
D000200:Action Potentials / Q000187:drug effects; D058646:Adrenergic alpha-1 Receptor Agonists; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020746:Calcium Channels, L-Type; D006332:Cardiomegaly / Q000503:physiopathology*; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006352:Heart Ventricles; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
D058646:Adrenergic alpha-1 Receptor Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D018340:Receptors, Adrenergic, alpha-1; D015222:Sodium Channels; D010656:Phenylephrine; D001464:Barium; D011433:Propranolol; D011224:Prazosin