Studer R, Reinecke H, Vetter R, Holtz J, Drexler H
Universitätsklinik Innere Medizin III Kardiologie und Angiologie, Freiburg, Germany.
Basic Res Cardiol. 1997;92 Suppl 1:53-8. doi: 10.1007/BF00794068.
The diastolic and systolic dysfunction in the failing heart appear to be related to the altered Ca2+ handling of the cardiac myocyte. Disturbed Ca2+ handling might also affect influx and efflux of other ions, including Na+. In this context, the cardiac sarcolemmal Na+/Ca2+ exchanger represents an important exchange mechanism of Ca2+ versus Na+ transport across the sarcolemma. Expression and function of cardiac Na+/Ca2+ exchanger is highest in newborn rats and declines gradually in postnatal development. In pressure overload-induced hypertrophy, expression of cardiac Na+/Ca2+ exchanger is increased and translated into increased Na+/Ca2+ exchanger activity similar to the early phase of postnatal development in the rat. This suggests a common underlying mechanism in the control of Na+/ Ca2+ exchanger expression in the immature and the hypertrophied myocardium. Similar to experimental-induced hypertrophy, mRNA, protein and activity of Na+/ Ca2+ exchanger is increased in the failing human heart suggesting an increase in the number of functional exchanger molecules rather than an enhanced exchange rate by preexisting exchanger molecules. The potential functional implications of an increased cardiac Na+/Ca2+ exchanger activity in human heart failure may be limitation of diastolic intracellular Ca2+ overload. However, this may increase the arrhythmogenic potential of the failing heart, since additional Na+ influx via Na+/Ca2+ exchanger may affect the membrane potential.
衰竭心脏中的舒张功能障碍和收缩功能障碍似乎与心肌细胞钙处理改变有关。钙处理紊乱也可能影响包括钠离子在内的其他离子的流入和流出。在这种情况下，心肌肌膜钠钙交换体是钙离子与钠离子跨肌膜转运的重要交换机制。心肌钠钙交换体的表达和功能在新生大鼠中最高，并在出生后发育过程中逐渐下降。在压力超负荷诱导的心肌肥大中，心肌钠钙交换体的表达增加，并转化为钠钙交换体活性增加，类似于大鼠出生后发育的早期阶段。这表明在未成熟心肌和肥大心肌中，钠钙交换体表达的调控存在共同的潜在机制。与实验性诱导的心肌肥大相似，在衰竭的人类心脏中，钠钙交换体的mRNA、蛋白质和活性增加，这表明功能性交换体分子数量增加，而不是现有交换体分子的交换速率提高。人类心力衰竭时心肌钠钙交换体活性增加的潜在功能意义可能是限制舒张期细胞内钙超载。然而，这可能会增加衰竭心脏的致心律失常潜力，因为通过钠钙交换体额外的钠离子内流可能会影响膜电位。
