Department of Physiology, Graduate School of Medical & Dental Sciences, Kagoshima University, Sakura-ga-oka, Kagoshima 890-8544, Japan.
Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110012, China.
Int J Mol Sci. 2023 Mar 29;24(7):6409. doi: 10.3390/ijms24076409.
Cav1.2 Ca channels, a type of voltage-gated L-type Ca channel, are ubiquitously expressed, and the predominant Ca channel type, in working cardiac myocytes. Cav1.2 channels are regulated by the direct interactions with calmodulin (CaM), a Ca-binding protein that causes Ca-dependent facilitation (CDF) and inactivation (CDI). Ca-free CaM (apoCaM) also contributes to the regulation of Cav1.2 channels. Furthermore, CaM indirectly affects channel activity by activating CaM-dependent enzymes, such as CaM-dependent protein kinase II and calcineurin (a CaM-dependent protein phosphatase). In this article, we review the recent progress in identifying the role of apoCaM in the channel 'rundown' phenomena and related repriming of channels, and CDF, as well as the role of Ca/CaM in CDI. In addition, the role of CaM in channel clustering is reviewed.
Cav1.2 钙通道是一种电压门控 L 型钙通道，广泛表达，是工作心肌细胞中主要的钙通道类型。Cav1.2 通道受与钙调蛋白（CaM）的直接相互作用调节，CaM 是一种 Ca2+结合蛋白，可导致钙依赖性易化（CDF）和失活（CDI）。无 Ca2+的 CaM（apoCaM）也有助于 Cav1.2 通道的调节。此外，CaM 通过激活 CaM 依赖性酶（如 CaM 依赖性蛋白激酶 II 和钙调神经磷酸酶（一种 CaM 依赖性蛋白磷酸酶））间接影响通道活性。在本文中，我们回顾了最近在确定 apoCaM 在通道“衰退”现象及相关通道重新激活、CDF 中的作用，以及 Ca/CaM 在 CDI 中的作用方面的研究进展。此外，还回顾了 CaM 在通道聚类中的作用。
