Defective excitation-contraction coupling in experimental cardiac hypertrophy and heart failure

被引:639
作者
Gomez, AM
Valdivia, HH
Cheng, H
Lederer, MR
Santana, LF
Cannell, MB
McCune, SA
Altschuld, RA
Lederer, WJ
机构
[1] UNIV MARYLAND, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21201 USA
[2] UNIV MARYLAND, SCH MED, CTR MED BIOTECHNOL, BALTIMORE, MD 21201 USA
[3] UNIV WISCONSIN, SCH MED, DEPT PHYSIOL, MADISON, WI 53706 USA
[4] NIA, SECT CARDIOVASC RES, BALTIMORE, MD 21224 USA
[5] UNIV LONDON ST GEORGES HOSP, SCH MED, DEPT PHARMACOL & CLIN PHARMACOL, LONDON SW17 0RE, ENGLAND
[6] OHIO STATE UNIV, DEPT FOOD SCI & TECHNOL, COLUMBUS, OH 43210 USA
[7] OHIO STATE UNIV, DEPT MED BIOCHEM, COLUMBUS, OH 43210 USA
基金
英国惠康基金;
关键词
D O I
10.1126/science.276.5313.800
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cardiac hypertrophy and heart failure caused by high blood pressure were studied in single myocytes taken from hypertensive rats (Dahl SS/Jr) and SH-HF rats in heart failure. Confocal microscopy and patch-clamp methods were used to examine excitation-contraction (EC) coupling, and the relation between the plasma membrane calcium current (I-Ca) and evoked calcium release from the sarcoplasmic reticulum (SR), which was visualized as ''calcium sparks.'' The ability of I-Ca to trigger calcium release from the SR in both hypertrophied and failing hearts was reduced. Because I-Ca density and SR calcium-release channels were normal, the defect appears to reside in a change in the relation between SR calcium-release channels and sarcolemmal calcium channels. beta-Adrenergic stimulation largely overcame the defect in hypertrophic but not failing heart cells. Thus, the same defect in EC coupling that develops during hypertrophy may contribute to heart failure when compensatory mechanisms fail.
引用
收藏
页码:800 / 806
页数:7
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