The L-type calcium channel current is increased by alpha-1 adrenoceptor activation in neonatal rat ventricular cells.
The activation of alpha-1 adrenoceptors in adult rat ventricular cells results in the reduction of the transient outward K+ current, but does not affect Ca++ currents. In this study, using neonatal rat ventricular cells, the alpha-1 adrenergic receptor agonist phenylephrine increased the long-lasting (L-type) Ca++ channel current (dihydropyridine-sensitive) and the increase was concentration-dependent. Phenylephrine did not, however, modulate the transient-type (T-type) Ca++ channel current. The alpha-1 effect of phenylephrine was reversed or abolished by prazosin, an alpha-1 antagonist. The alpha-2 agonist clonidine had no effect on the L-type current. Yohimbine, an alpha-2 antagonist, and propranolol, a beta antagonist, did not inhibit the effect of phenylephrine on L-type current. The effect of phenylephrine was abolished by pretreatment with WB4101, an alpha-1A antagonist, but not by chloroethylclonidine, an alpha-1B antagonist. In addition, norepinephrine also increased the L-type current in the presence of propranolol and this effect was reversed by washout. These observations suggest that phenylephrine increased the L-type Ca++ channel current specifically through the activation of alpha-1A adrenergic receptors in neonatal rat ventricular myocytes. This may explain in part the increase in the plateau phase of the action potential and the positive inotropic response of the neonatal myocardium to phenylephrine. This is the first description of an increase in L-type Ca++ current by alpha-1A adrenoceptor activation in neonatal rat ventricular myocytes, and this effect is different from that reported in adult rat myocytes.
Department of Physiology, University of Alberta, Edmonton, Canada.
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Liu
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Karpinski
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology
D015220:Calcium Channels; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011433:Propranolol; D009638:Norepinephrine