Ca2+ removal mechanisms in mouse embryonic stem cell-derived cardiomyocytes
Ca2+ removal mechanisms in mouse embryonic stem cell-derived cardiomyocytes
复制标题
小鼠胚胎干细胞来源的心肌细胞中的 Ca2+ 去除机制
DOI：
10.1152/ajpcell.00025.2009
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发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Yang, Huang-Tian
中科院分区：
文献类型：
--
作者：
Guo, Ang;Yang, Huang-Tian
Guo A, Yang HT. Ca2+ removal mechanisms in mouse embryonic stem cell-derived cardiomyocytes. Am J Physiol Cell Physiol 297: C732-C741, 2009. First published July 15, 2009; doi:10.1152/ajpcell.00025.2009.-In mammalian adult cardiomyocytes, sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) plays a major role in controlling the decline of cytosolic free Ca2+ concentration ([Ca2+](i)) in comparison with sarcolemmal Na+/Ca2+ exchanger (NCX). However, the functional importance of SERCA and NCX in cytosolic Ca2+ removal during early cardiomyogenesis is still debated. In this study, the functional contributions of Ca2+ transporters to [Ca2+](i) decline in mouse embryonic stem cell-derived cardiomyocytes (mESCMs), a suitable model for investigation of early cardiogenesis, at various differentiation stages were investigated. We estimated that even at early differentiation stages of mESCMs, SERCA was responsible for similar to 76% of total Ca2+ removal, while NCX was responsible for similar to 21%. The contributions of SERCA and NCX to cytosolic Ca2+ clearance were increased to similar to 88% and decreased to similar to 10%, respectively, at the late differentiation stage. Dynamical analysis of the transient decay phases in normal and Na+-free solutions suggests that the contribution of NCX to [Ca2+](i) decline is more apparent in the terminal slow decay phase than that in the initial fast phase. When SR function was suppressed in type 2 ryanodine receptor-null mESCMs or with ryanodine receptor and SERCA inhibitors (ryanodine and thapsigargin), NCX acted as the main pathway for [Ca2+](i) decline. We conclude that the rapid [Ca2+](i) decline is mainly achieved by the SR uptake even at the early differentiation stage of mESCMs, while NCX acts as the main Ca2+ remover when SR function is suppressed. These findings suggest a critical role of SR in the regulation of [Ca2+](i) homeostasis even in differentiating cardiomyocytes.
