抄録
A change in intracellular Ca2+ concentration is an important process for cardiac excitation-contraction coupling. Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been identified as the one of the multifunctional and specialized proteins activated by cytoplasmic Ca2+ signaling in cardiomyocytes. Activated CaMKII targets several myocyte proteins such as Na+ channels, Ca2+ transport proteins (voltage-gated L-type Ca2+ channel, phosholamban and ryanodine receptor) and K+ channels, consequently controlling the membrane potential and modulating myoplasmic Ca2+ homeostasis. Recent studies have elucidated that cardiac adrenoceptor (AR) stimulation is one of the triggers for the activation of CaMKII. β-AR stimulation (which is the most prominent regulator of cardiac function) activates CaMKII by both a traditional Ca2+-dependent pathway (Gs-adenylyl cyclase-cAMP-PKA pathway) and by a more direct, Ca2+-independent pathway. Our recent finding is that α1-AR stimulation also activates CaMKII as in the case of β-AR signaling. We reported that (1) CaMKII is activated by α1A-AR-Gq-phospholipase C-l PKCs (δ and/or ε) pathway at transverse tubules and (2) activated CaMKII increases L-type Ca2+ current. In this presentation, we highlight the regulatory mechanisms of CaMKII activity by α1-AR stimulation and show a novel model for CaMKII regulation of L-type Ca2+ channel function by α1-AR stimulation. [J Physiol Sci. 2008;58 Suppl:S45]
