Walweel K, Laver D R
School of Biomedical Sciences and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, 2308, Australia.
Biophys Rev. 2015 Mar;7(1):33-41. doi: 10.1007/s12551-014-0152-4. Epub 2014 Dec 16.
Normal heart contraction and rhythm relies on the proper flow of calcium ions (Ca) into cardiac cells and between their intracellular organelles, and any disruption can lead to arrhythmia and sudden cardiac death. Electrical excitation of the surface membrane activates voltage-dependent L-type Ca channels to open and allow Ca to enter the cytoplasm. The subsequent increase in cytoplasmic Ca concentration activates calcium release channels (RyR2) located at specialised Ca release sites in the sarcoplasmic reticulum (SR), which serves as an intracellular Ca store. Animal models have provided valuable insights into how intracellular Ca transport mechanisms are altered in human heart failure. The aim of this review is to examine how Ca release sites are remodelled in heart failure and how this affects intracellular Ca transport with an emphasis on Ca release mechanisms in the SR. Current knowledge on how heart failure alters the regulation of RyR2 by Ca and Mg and how these mechanisms control the activity of RyR2 in the confines of the Ca release sites is reviewed.
正常的心脏收缩和节律依赖于钙离子（Ca）流入心肌细胞及其细胞内细胞器之间的适当流动，任何干扰都可能导致心律失常和心源性猝死。表面膜的电兴奋激活电压依赖性L型钙通道打开，使Ca进入细胞质。随后细胞质Ca浓度的增加激活位于肌浆网（SR）中特殊Ca释放位点的钙释放通道（RyR2），肌浆网作为细胞内Ca储存库。动物模型为了解人类心力衰竭时细胞内Ca转运机制如何改变提供了有价值的见解。本综述的目的是研究心力衰竭时Ca释放位点如何重塑，以及这如何影响细胞内Ca转运，重点是SR中的Ca释放机制。综述了目前关于心力衰竭如何改变Ca和Mg对RyR2的调节以及这些机制如何在Ca释放位点范围内控制RyR2活性的知识。
