Cellular Mechanism Underlying Burn Serum-Generated Bidirectional Regulation of Excitation-Contraction Coupling in Isolated Rat Cardiomyocytes
Cellular Mechanism Underlying Burn Serum-Generated Bidirectional Regulation of Excitation-Contraction Coupling in Isolated Rat Cardiomyocytes
复制标题
DOI：
10.1097/shk.0b013e3182000379
复制
发表时间：
2011-04
期刊：
影响因子：
3.1
通讯作者：
Xinping Luo;Jian-xin Deng;Na Liu;Cuicui Zhang;Qiaobing Huang;Jie Liu
中科院分区：
文献类型：
--
作者：
Xinping Luo;Jian-xin Deng;Na Liu;Cuicui Zhang;Qiaobing Huang;Jie Liu
Myocardial depressant factors have long been recognized to be present in burn serum (BS) and contribute to burn-generated cardiac contractile dysfunction. However, much of the cellular and molecular mechanism for its role in the development of the cardiac deficiency remains unknown. In this study, we investigated the effect of BS on myocardial contractility and Ca2+ handling in single rat cardiomyocytes. The results revealed that BS (5% by volume) bidirectionally regulated cardiac excitation-contraction (EC) coupling. The action potential-elicited Ca2+ transient and cell shortening were increased by 28.0% ± 9.7% and 34.7% ± 12.5% within 20 min after BS stimulation (the upregulation phase), but decreased by 20.5% ± 6.8% and 32.3% ± 5.1% at 60 min after BS stimulation (the downregulation phase). There was a 32.0% ± 5.8% reduction in sarcoplasmic reticulum (SR) Ca2+ content at the downregulation phase, whereas no alteration was detected at the upregulation phase. The incidences of spontaneous Ca2+ sparks and Ca2+ waves were significantly increased after BS stimulation, no matter at the upregulation or downregulation phase. The hyperactive Ca2+ sparks and Ca2+ waves could be completely abolished by antioxidative treatment (vitamin A, 0.2 mM; and vitamin E, 1 mM) and partially reversed by NOS inhibitor L-NAME (100 M), but not by blocking Ca2+ influx with nifedipine (1 M). With the normalization of Ca2+ sparks, BS-induced alterations of action potential-elicited Ca2+ transient and contractility were prevented by antioxidative therapy. Taken together, we propose that BS-associated bidirectional regulation of EC coupling is attributed largely to oxidative stress-induced hyperactivity of ryanodine receptors, increasing EC coupling through enhancing intracellular Ca2+ release initially, but subsequently decreasing EC coupling by partially depleting SR Ca2+ content through enhancement of Ca2+ spark-mediated SR leak.
