Abstract
Purpose: We have recently reported that the effects of α1-adrenoceptor stimulation (α1ARS) on L-type Ca2+ current (ICa) can be classified in two opposite effects (negative and positive effects) and the positive effect is protein kinase C (PKC)-dependent. We postulate that these two effects simultaneously occur through different subtypes of α1-adrenoceptor and different intracellular signal transduction pathways. In this study, we investigated the effects of α1AARS and α1BARS on ICa. Methods: Perforated patch-clamp was used for recording of ICa from isolated adult rat ventricular myocytes. Holding potential was set at -40 mV and depolarization pulse to 0 mV was applied every 10 sec. Results: Biphasic change in ICa (a transient decrease followed by a sustained increase) was induced by a non-selective α1-adrenoceptor agonist, phenylephrine (Phe). However, a selective α1A agonist, A61603 showed only positive effect on ICa, and the application of Phe with a selective α1A antagonist, WB4101, caused only sustained negative effect. After pertussis toxin treatment, a transient decrease in ICa induced by Phe disappeared and only sustained increase was observed. Conclusion α1AARS showed positive effect on ICa, which was PKC-dependent. On the other hand, α1BARS showed negative effect mediated through Gi/o protein. Thus, α1AARS and α1BARS produce opposite effects on ICa via different intracellular signal transduction pathways. [J Physiol Sci. 2006;56 Suppl:S127]