alpha1-Adrenergic activation of L-type Ca current in rat ventricular myocytes: perforated patch-clamp recordings.
alpha1-Adrenergic stimulation has little effect on L-type Ca2+ channel current (ICa,L) in adult cardiac myocytes measured using conventional whole cell voltage-clamp techniques. In this study using perforated-patch techniques, we reevaluated the effect of alpha1-adrenergic stimulation on ICa,L in adult rat ventricular myocytes. Action potentials and ICa,L were examined in the presence of 1 microM nadolol, a beta-adrenergic antagonist, in myocytes internally dialyzed with Na+- and K+-free solutions (Cs+ and tetraethylammonium as substitutes). Phenylephrine (PE; 30 microM) increased the action potential duration measured at 25 and 70% of repolarization by 104 and 86%, respectively. In the perforated-patch configuration, PE elicited a transient decrease followed by a approximately 60% increase in ICa,L, whereas only the transient decrease in ICa,L was observed in myocytes when the conventional whole cell configuration was used. The PE-induced increase in ICa,L was reversibly blocked by 1 microM prazosin, an alpha1-adrenergic antagonist. These results suggest that alpha1-adrenergic stimulation enhances cardiac ICa,L and that obligatory intracellular mediators for this action are lost during whole cell recordings.
Liu
S J
SJ
Department of Biopharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Kennedy
R H
RH
D000200:Action Potentials / Q000187:drug effects*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D009206:Myocardium / Q000166:cytology*; D009248:Nadolol / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D010656:Phenylephrine; D009248:Nadolol