From the Department of Molecular Cardiology and Epigenetics (M.D., A.v.d.L., J.B.) and Department of Cardiology (H.A.K.), Heidelberg University, Germany; and DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, Germany (M.D., A.v.d.L., H.A.K., J.B.).
Circ Res. 2017 Sep 29;121(8):1000-1020. doi: 10.1161/CIRCRESAHA.117.310355.
Calcium (Ca) is a universal regulator of various cellular functions. In cardiomyocytes, Ca is the central element of excitation-contraction coupling, but also impacts diverse signaling cascades and influences the regulation of gene expression, referred to as excitation-transcription coupling. Disturbances in cellular Ca-handling and alterations in Ca-dependent gene expression patterns are pivotal characteristics of failing cardiomyocytes, with several excitation-transcription coupling pathways shown to be critically involved in structural and functional remodeling processes. Thus, targeting Ca-dependent transcriptional pathways might offer broad therapeutic potential. In this article, we (1) review cytosolic and nuclear Ca dynamics in cardiomyocytes with respect to their impact on Ca-dependent signaling, (2) give an overview on Ca-dependent transcriptional pathways in cardiomyocytes, and (3) discuss implications of excitation-transcription coupling in the diseased heart.
钙(Ca)是各种细胞功能的普遍调节剂。在心肌细胞中,Ca 是兴奋-收缩偶联的核心要素,但也会影响多种信号级联,并影响基因表达的调节,称为兴奋-转录偶联。细胞内 Ca 处理的紊乱和 Ca 依赖性基因表达模式的改变是衰竭心肌细胞的主要特征,有几个兴奋-转录偶联途径被证明在结构和功能重塑过程中起着至关重要的作用。因此,靶向 Ca 依赖性转录途径可能具有广泛的治疗潜力。在本文中,我们(1)回顾了心肌细胞中胞质和核内 Ca 动力学及其对 Ca 依赖性信号的影响,(2)概述了心肌细胞中 Ca 依赖性转录途径,(3)讨论了兴奋-转录偶联在患病心脏中的意义。