Mechanisms underlying the regulation of L-type Ca²⁺ current during alpha₁-adrenoceptor stimulation in adult rat ventricular myocytes

Abstract

In ventricular myocytes, α₁-adrenoceptor stimulation (α₁ARS) increases L-type Ca²⁺ current (I_Ca,L) in perforated patch clamp (PP) recording but not in conventional whole cell recording. We hypothesized Ca²⁺-related protein kinase such as Ca2+/calmodulin-dependent protein kinase II (CaMKII) or protein kinase C (PKC) is involved in the regulation of I_Ca,L during α₁ARS. In this study, we investingated the effect of phenylephrine (Phe) on I_Ca,L in adult rat ventricular myocytes using PP recording. As previous studies, we observed biphasic modulation in I_Ca,L by 10 μM Phe; a transient decrease followed by a sustained increase. However, 1 μM Phe just increased I_Ca,L. In the presence of CaMKII inhibitor 0.5 μM KN-93, a CaMKII inhibitor, 10 μM Phe produced only a sustained negative phase of I_Ca,L while 1 μM Phe did not alter I_Ca,L. In the presence of 10 μM chelerythrine, a PKC inhibitor, 10 μM Phe produced only a sustained negative phase as in the presence of CAMKII inhibitor. Our result suggests that (1) the effect of α₁ARS on I_Ca,L can be classified into two phases (negative phase and positive phase) which have different concentration-dependence and (2) CaMKII and PKC regulate the positive phase of I_Ca,L during α₁ARS. [Jpn J Physiol 54 Suppl:S96 (2004)]