文章基本信息

标题：The mitochondrial Na⁺-Ca²⁺ exchanger, NCLX, regulates automaticity of HL-1 cardiomyocytes
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作者：Ayako Takeuchi ; Bongju Kim ; Satoshi Matsuoka 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2013
卷号：3
DOI：10.1038/srep02766
出版社：Springer Nature
摘要：Mitochondrial Ca²⁺ is known to change dynamically, regulating mitochondrial as well as cellular functions such as energy metabolism and apoptosis. The NCLX gene encodes the mitochondrial Na⁺-Ca²⁺ exchanger (NCX_mit), a Ca²⁺ extrusion system in mitochondria. Here we report that the NCLX regulates automaticity of the HL-1 cardiomyocytes. NCLX knockdown using siRNA resulted in the marked prolongation of the cycle length of spontaneous Ca²⁺ oscillation and action potential generation. The upstrokes of action potential and Ca²⁺ transient were markedly slower, and sarcoplasmic reticulum (SR) Ca²⁺ handling were compromised in the NCLX knockdown cells. Analyses using a mathematical model of HL-1 cardiomyocytes demonstrated that blocking NCX_mit reduced the SR Ca²⁺ content to slow spontaneous SR Ca²⁺ leak, which is a trigger of automaticity. We propose that NCLX is a novel molecule to regulate automaticity of cardiomyocytes via modulating SR Ca²⁺ handling.