Laboratory of Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, BE3000 Leuven, Belgium.
Cold Spring Harb Perspect Biol. 2020 Mar 2;12(3):a035428. doi: 10.1101/cshperspect.a035428.
Rhythmic increases in intracellular Ca concentration underlie the contractile function of the heart. These heart muscle-wide changes in intracellular Ca are induced and coordinated by electrical depolarization of the cardiomyocyte sarcolemma by the action potential. Originating at the sinoatrial node, conduction of this electrical signal throughout the heart ensures synchronization of individual myocytes into an effective cardiac pump. Ca signaling pathways also regulate gene expression and cardiomyocyte growth during development and in pathology. These fundamental roles of Ca in the heart are illustrated by the prevalence of altered Ca homeostasis in cardiovascular diseases. Indeed, heart failure (an inability of the heart to support hemodynamic needs), rhythmic disturbances, and inappropriate cardiac growth all share an involvement of altered Ca handling. The prevalence of these pathologies, contributing to a third of all deaths in the developed world as well as to substantial morbidity makes understanding the mechanisms of Ca handling and dysregulation in cardiomyocytes of great importance.
细胞内钙离子浓度的有节奏增加是心脏收缩功能的基础。这种心肌细胞内钙离子的广泛变化是由动作电位引起的心肌细胞膜去极化引起和协调的。起源于窦房结,这种电信号在心脏中的传导确保了单个心肌细胞的同步有效心脏泵功能。钙信号通路还调节发育过程中和病理学中的基因表达和心肌细胞生长。钙在心脏中的这些基本作用,通过心血管疾病中钙稳态的改变的普遍性来体现。事实上,心力衰竭(心脏无法支持血液动力学需求)、节律紊乱和不当的心脏生长都与钙处理的改变有关。这些病理的普遍性,导致了发达世界三分之一的死亡以及大量的发病率,使得理解心肌细胞中钙处理和调节失常的机制变得非常重要。