Calcium overload and cardiac function

被引:132
作者
Vassalle, M
Lin, CI
机构
[1] SUNY Downstate Med Ctr, Dept Physiol & Pharmacol, Brooklyn, NY 11203 USA
[2] Natl Def Med Ctr, Dept Physiol & Biophys, Taipei, Taiwan
基金
美国国家卫生研究院;
关键词
calcium overload; cardiac arrhythmias; cardiac contraction; cardiac failure; digitalis;
D O I
10.1159/000079666
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca2+ may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca2+ overload include arrhythmias caused by oscillatory (V-os) and non-oscillatory (V-ex) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na+ in electrical abnormalities as a charge carrier in the Na+-Ca2+ exchange and a role of Ca2+ in mechanical toxicity. Ca2+ overload may be induced by an increase in [Na+](i) through the inhibition of the Na+-K+ pump (e.g. toxic concentrations of digitalis) or by an increase in Ca2+ load (e.g. catecholamines). The Ca2+ overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca2+ overload than myocardial fibers, possibly because of their greater Na+ load. If the SR is predominantly Ca2+ overloaded, V-os and fast discharge are induced through an oscillatory release of Ca2+ in diastole from the SR; if the cytoplasm is Ca2+ overloaded, the non-oscillatory V-ex tail is induced at negative potentials. The decrease in contractile force by Ca2+ overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents I-os and I-ex underlie V-os and V-ex, respectively, both being due to an electrogenic extrusion of Ca2+ through the Na+-Ca2+ exchange. I-os is an oscillatory current due to an oscillatory release of Ca2+ in early diastole from the Ca2+-overloaded SR, and I-ex is a non-oscillatory current due to the extrusion of Ca2+ from the Ca2+-overloaded cytoplasm. I-os and I-ex can be present singly or simultaneously. An increase in [Ca2+](i) appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca2+](i) may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca2+-overloaded cardiac cells by decreasing the inhibition of the Na+-K+ pump by Ca2+, thereby leading to a reduction in Ca2+ overload and to an increase in force of contraction. Copyright (C) 2004 National Science Council, ROC and S. Karger AG, Basel.
引用
收藏
页码:542 / 565
页数:24
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