The mitochondrial Na+-Ca2+ exchanger, NCLX, regulates automaticity of HL-1 cardiomyocytes.
Mitochondrial Ca(2+) 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(+)-Ca(2+) exchanger (NCXmit), a Ca(2+) 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 Ca(2+) oscillation and action potential generation. The upstrokes of action potential and Ca(2+) transient were markedly slower, and sarcoplasmic reticulum (SR) Ca(2+) handling were compromised in the NCLX knockdown cells. Analyses using a mathematical model of HL-1 cardiomyocytes demonstrated that blocking NCXmit reduced the SR Ca(2+) content to slow spontaneous SR Ca(2+) leak, which is a trigger of automaticity. We propose that NCLX is a novel molecule to regulate automaticity of cardiomyocytes via modulating SR Ca(2+) handling.
1] Department of Physiology and Biophysics, Graduate School of Medicine, Kyoto University, Yoshida-konoe, Sakyo-ku, Kyoto 606-8501, Japan [2].
Ayako
A
Takeuchi
Bongju
B
Kim
Satoshi
S
Matsuoka
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D003198:Computer Simulation; D055785:Gene Knockdown Techniques; D007700:Kinetics; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D014162:Transfection
D034741:RNA, Small Interfering; C588042:Slc8b1protein, mouse; D019831:Sodium-Calcium Exchanger; D002118:Calcium