Dyssynchronous Ca2+ sparks in myocytes from infarcted hearts
Dyssynchronous Ca2+ sparks in myocytes from infarcted hearts
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DOI：
10.1161/01.res.87.11.1040
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发表时间：
2000-11-24
影响因子：
20.1
通讯作者：
Bridge, JHB
中科院分区：
文献类型：
--
作者：
Litwin, SE;Zhang, DF;Bridge, JHB
在衰竭心脏的心肌细胞中，收缩和钙瞬变的动力学是缓慢的。造成这些异常的机制尚不清楚。结扎家兔旋支动脉造成心肌梗死(MI)。我们使用共聚焦显微镜记录了来自对照和梗死心脏(3周)的左心室(LV)心肌细胞在场刺激过程中空间分辨的钙瞬变。与对照组相比，梗死灶旁心肌细胞内钙瞬变的峰值较低，时间较长。对照心肌细胞在电刺激后，细胞内钙离子的变化相对均匀。相反，在心肌梗死细胞中，[Ca~(2+)]不均匀地升高，并且在整个钙瞬变的上升和下降阶段都有局部的[Ca~(2+)]升高。心肌梗死组和对照组肌浆网钙离子含量差异无统计学意义。心肌梗死细胞L型钙电流密度峰值降低。当以钙瞬变/峰值钙的幅度计算时，对照组和心肌梗死组的宏观增益函数没有差别。然而，当计算为钙瞬变/峰值I-Ca升高的峰值速率时，心肌梗死细胞的增益函数略有下降。应用异丙肾上腺素(100nmol/L)可促进心肌梗死细胞在0.5和1 Hz时钙释放的同步性。心肌梗死后心肌细胞内钙火花的不协调产生可能是宏观钙瞬变减弱和减慢的原因之一。当β-肾上腺素能刺激增强钙循环蛋白的磷酸化时，这些异常可以在很大程度上被克服。
The kinetics of contractions and Ca2+ transients are slowed in myocytes from failing hearts. The mechanisms accounting for these abnormalities remain unclear. Myocardial infarction (MI) was produced by ligation of the circumflex artery in rabbits. We used confocal microscopy to record spatially resolved Ca2+ transients during field stimulation in left ventricular (LV) myocytes from control and infarcted hearts (3 weeks). Compared with controls, Ca2+ transients in myocytes adjacent to the infarct had lower peak amplitudes and prolonged time courses. Control myocytes showed relatively uniform changes in [Ca2+] throughout the cell after electrical stimulation. In contrast, in MI myocytes [Ca2+] increased inhomogeneously and localized increases in [Ca2+] occurred throughout the rising and falling phases of the Ca2+ transient. Ca2+ content of the sarcoplasmic reticulum did not differ between MI and control myocytes. Peak L-type Ca2+ current density was reduced in MI myocytes. The macroscopic gain function was not different in control and MI myocytes when calculated as the amplitude of the Ca2+ transient/peak I-Ca. However, when calculated as the peak rate of rise of the Ca2+ transient/peak I-Ca he gain function was modestly decreased in the MI myocytes. Application of isoproterenol (100 nmol/L) improved the synchronization of Ca2+ release in MI myocytes at both 0.5 and 1 Hz. The poorly coordinated production of Ca2+ sparks in myocytes from infarcted rabbit hearts likely contributes to the diminished and slowed macroscopic Ca2+ transient. These abnormalities can be largely overcome when phosphorylation of Ca2+ cycling proteins is enhanced by beta -adrenergic stimulation.