Dyssynchronous Ca2+ sparks in myocytes from infarcted hearts

被引:156
作者
Litwin, SE
Zhang, DF
Bridge, JHB
机构
[1] Vet Affairs Med Ctr, Div Cardiol, Salt Lake City, UT 84148 USA
[2] Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA
[3] Nora Eccles Harrison Cardiovasc & Res Training In, Salt Lake City, UT USA
关键词
myocardial infarction; calcium channels; heart failure; sarcoplasmic reticulum; sparks;
D O I
10.1161/01.RES.87.11.1040
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1040 / 1047
页数:8
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