Effects ofα1-adrenergic Stimulation on L-type Ca2+Current in Rat Ventricular Myocytes

The effect ofα1-adrenergic stimulation on -type Ca2+current (ICa,L) in adult rat ventricular myocytes was investigated using three different methods of current recording. During conventional whole-cell recordings with 5 m -BAPTA included in the pipette solution, phenylephrine (20μm) did not increase ICa,Lafter 10 min of application. With nystatin perforated-patch whole-cell recordings, phenylephrine potentiated ICa,L, although there were variations among myocytes. The most frequent response was a transient suppression of peak ICa,Lat 2 min of exposure followed by a sustained increase of current amplitude evident after 5–10 min exposure. The relative current amplitude 10 min after phenylephrine application was 1.08±0.05 compared to control (n=14 cells,P<0.05). During cell-attached single channel recordings, phenylephrine (1μm) increased the -type Ca2+channel open probability (NPo) by 2.25±0.31-fold (n=21,P<0.01). It potentiated NPoby increasing the number of openings per sweep and also by promoting longer openings. These effects developed slowly in 10 min. Phenylephrine had no effect on unitary current amplitude. The potentiation was also elicited by methoxamine (5μm) and was blocked by prazosin (1μm), indicating that it was mediated byα1-adrenergic receptor stimulation. The increase in NPowas suppressed by chelerythrine, a protein kinase C inhibitor. Our results demonstrate that ICa,Lcan be enhanced byα1-adrenergic stimulation, and stress the importance of not disturbing the intracellular environment during studies of the modulation of cardiac ICa,Lbyα1-adrenergic stimulation.