Effects of phenylephrine on calcium current and contractility of feline ventricular myocytes.
Previous studies on numerous cardiac preparations have shown that stimulation of alpha 1-receptors produces a positive inotropic effect. The cellular basis for this effect is not well understood. Isolated feline ventricular myocytes were used in the present study to examine the idea that the increase in contractility induced by stimulation of alpha 1-receptors is produced by an increase in inward Ca2+ current and that this event is caused by the stimulation of protein kinase C (PKC). These experiments showed that phenylephrine (10(-4) M) increased Ca2+ current from 0.56 +/- 0.02 (control) to 1.12 +/- 0.25 nA and increased contractile magnitude by 201 +/- 28%. The effect on Ca2+ current was completely blocked by propranolol (10(-7)M), whereas after beta-receptor blockade, contractile state was still 130 +/- 8% of control levels. alpha 1-Receptor blockade by prazosin eliminated this residual inotropic component of phenylephrine. Lower concentrations of phenylephrine (10(-7)M) were without effect on Ca2+ current and contractility as was stimulation of PCK with 150 nM of a phorbol ester. These results suggest that the positive inotropic effect of alpha 1-receptor stimulation in adult feline ventricular myocytes is not produced by increasing inward Ca2+ current and that this response is also not associated with stimulation of PKC.
Hartmann
H A
HA
Temple University School of Medicine, Department of Physiology, Philadelphia, Pennsylvania 19140.
Mazzocca
N J
NJ
Kleiman
R B
RB
Houser
S R
SR
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015220:Calcium Channels; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D004533:Egtazic Acid; D011433:Propranolol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011224:Prazosin