POSTISCHEMIC CHANGES IN CARDIAC SARCOPLASMIC-RETICULUM CA2+ CHANNELS - A POSSIBLE MECHANISM OF ISCHEMIC PRECONDITIONING

被引:83
作者
ZUCCHI, R
RONCATESTONI, S
YU, GY
GALBANI, P
RONCA, G
MARIANI, M
机构
[1] UNIV PISA, IST CARDIOL, I-56100 PISA, ITALY
[2] UNIV PISA, IST CHIM BIOL, I-56100 PISA, ITALY
关键词
SARCOPLASMIC RETICULUM; CA2+; ISCHEMIA; REPERFUSION;
D O I
10.1161/01.RES.76.6.1049
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We investigated the modifications of cardiac ryanodine receptors/sarcoplasmic reticulum Ca2+ release channels occurring in ischemic preconditioning. In an isolated rat heart model, the injury produced by 30 minutes of global ischemia was reduced by preexposure to three 3-minute periods of global ischemia (preconditioning ischemia). The protection was still present 120 minutes after preconditioning ischemia but disappeared after 240 minutes. Three 1-minute periods of global ischemia did not provide any protection. In the crude homogenate obtained from ventricular myocardium, the density of [H-3]ryanodine binding sites averaged 372+/-18 fmol/mg of protein in the control condition, decreased 5 minutes after preconditioning ischemia (290+/-15 fmol/mg, P<.01), was still significantly reduced after 120 minutes (298+/-17 fmol/mg,, P<.05), and recovered after 240 minutes (341+/-21 fmol/mg). Three 1-minute periods of ischemia did not produce any change in ryanodine binding. The K-d for ryanodine (1.5+/-0.3 nmol/L) was unchanged in all cases. In parallel experiments, the crude homogenate or a microsomal fraction was passively loaded with Ca-45, and Ca2+-induced Ca2+ release was studied by the quick filtration technique. In both preparations, the rate constant of Ca2+-induced Ca2+ release decreased 5 and 120 minutes after preconditioning ischemia (homogenate values: 19.7+/-1.4 and 18.9+/-0.9 s(-1) vs a control value of 25.4+/-1.7 s(-1) P<.05 in both cases) and recovered after 240 minutes (23.0+/-1.9 s(-1)). The Ca2+ dependence of Ca2+-induced Ca2+ release was not affected by preconditioning ischemia. In conclusion, changes in sarcoplasmic reticulum Ca2+-release channels occur after brief ischemia and reperfusion, are closely correlated with the development of myocardial protection Versus sustained ischemia, and might play a role in the pathogenesis of ischemic preconditioning.
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页码:1049 / 1056
页数:8
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