Abstract
Introduction: The sympathetic nervous system modulates cardiac L-type Ca2+ channels through α1- and β-adrenoceptors (ARs). We previously showed that α1-AR stimulation alone potentiates L-type Ca2+ current (ICa) through α1A-AR-Gq-PLC-PKC-CaMKII pathway (O-Uchi J. et al., PNAS, 2005 and J. Physiol. Sci., 2006 (Suppl)). However, the interaction of α1- and β-AR signalings on ICa was not fully clarified. In the present study, we investigated the effect of α1-AR stimulation on ICa in the presence of β-AR stimulation. Methods: Perforated patch was employed for recording ICa from isolated adult rat ventricular myocytes. Cells were at first superfused with 100 nM isoproterenol (Iso) for β-AR stimulation and then α1-AR agonists were applied in the continuous presence of Iso. Results: The Iso-stimulated ICa was markedly inhibited by an α1-AR agonist, 100 μM phenylephrine (Phe) (19.6±7.6%) (n=7). This effect was abolished by the application of an α1-AR antagonist, 1 μM prazosin. The α1A-AR selective antagonist, 2 μM WB4101 or 100 nM 5-methylurapidil also blocked this inhibitory effect, but an α1B-AR selective antagonist, 100 nM L-765,314 did not. The α1A-AR selective agonist, 100 nM A61603 showed 18.3±6.7% inhibition of Iso-stimulated ICa (n=7) as in the case of Phe, confirming that α1A-AR is involved in this mechanism. Conclusion: α1A-AR stimulation inhibits ICa in the presence of β-AR stimulation, which is opposite to the effect observed in the absence of β-AR stimulation. [J Physiol Sci. 2008;58 Suppl:S180]
