Vassalle Mario, Lin Cheng-I
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
J Biomed Sci. 2004 Sep-Oct;11(5):542-65. doi: 10.1007/BF02256119.
The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca(2+) 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 Ca(2+) 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(+)-Ca(2+) exchange and a role of Ca(2+) in mechanical toxicity. Ca(2+) overload may be induced by an increase in Na(+) through the inhibition of the Na(+)-K(+) pump (e.g. toxic concentrations of digitalis) or by an increase in Ca(2+) load (e.g. catecholamines). The Ca(2+) overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca(2+) overload than myocardial fibers, possibly because of their greater Na(+) load. If the SR is predominantly Ca(2+) overloaded, V(os) and fast discharge are induced through an oscillatory release of Ca(2+) in diastole from the SR; if the cytoplasm is Ca(2+) overloaded, the non-oscillatory V(ex) tail is induced at negative potentials. The decrease in contractile force by Ca(2+) 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 Ca(2+) through the Na(+)-Ca(2+) exchange. I(os) is an oscillatory current due to an oscillatory release of Ca(2+) in early diastole from the Ca(2+)-overloaded SR, and I(ex) is a non-oscillatory current due to the extrusion of Ca(2+) from the Ca(2+)-overloaded cytoplasm. I(os) and I(ex) can be present singly or simultaneously. An increase in Ca(2+) appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, Ca(2+) may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca(2+)-overloaded cardiac cells by decreasing the inhibition of the Na(+)-K(+) pump by Ca(2+), thereby leading to a reduction in Ca(2+) overload and to an increase in force of contraction.
本文综述了钙超载引起的心脏功能变化。细胞内Ca(2+)可在不同结构（如肌浆网、细胞质和线粒体）中升高至过量水平，从而诱发心脏组织的电活动和机械活动异常。Ca(2+)超载的电表现包括由振荡电位（V(os)）和非振荡电位（V(ex)）引起的心律失常。机械表现包括收缩力下降、挛缩和后收缩。潜在机制包括Na(+)在电异常中作为Na(+)-Ca(2+)交换中的电荷载体所起的作用，以及Ca(2+)在机械毒性中所起的作用。Ca(2+)超载可通过抑制Na(+)-K(+)泵导致细胞内[Na(+)]升高（如洋地黄中毒浓度）或通过增加Ca(2+)负荷（如儿茶酚胺）诱发。快速心率可增强Ca(2+)超载。浦肯野纤维比心肌纤维更容易受到Ca(2+)超载的影响，可能是因为它们的Na(+)负荷更大。如果肌浆网主要发生Ca(2+)超载，舒张期Ca(2+)从肌浆网振荡释放可诱发V(os)和快速放电；如果细胞质发生Ca(2+)超载，则在负电位时诱发非振荡性V(ex)尾电流。Ca(2+)超载导致的收缩力下降似乎与高能磷酸盐减少有关，因为代谢抑制剂可增强这种作用，而代谢底物可减轻这种作用。离子电流I(os)和I(ex)分别是V(os)和V(ex)的基础，两者均由Ca(2+)通过Na(+)-Ca(2+)交换的电致性外排引起。I(os)是一种振荡电流，由于舒张早期Ca(2+)从Ca(2+)超载的肌浆网中振荡释放所致，而I(ex)是一种非振荡电流，由于Ca(2+)从Ca(2+)超载的细胞质中外排所致。I(os)和I(ex)可单独或同时出现。细胞内[Ca(2+)]升高似乎参与了生理和病理条件下倾向于维持心输出量的短期和长期代偿机制。最终，细胞内[Ca(2+)]可能升高至超载水平并导致心力衰竭。实验证据表明，临床浓度的洋地黄通过减少Ca(2+)对Na(+)-K(+)泵的抑制作用，增加Ca(2+)超载心脏细胞的收缩力，从而导致Ca(2+)超载减少和收缩力增加。
