Hobai I A, O'Rourke B
Institute of Molecular Cardiobiology, Division of Cardiology, Department of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA.
Circ Res. 2000 Oct 13;87(8):690-8. doi: 10.1161/01.res.87.8.690.
Defective excitation-contraction coupling in heart failure is generally associated with both a reduction in sarcoplasmic reticulum (SR) Ca(2+) uptake and a greater dependence on transsarcolemmal Na(+)-Ca(2+) exchange (NCX) for Ca(2+) removal. Although a relative increase in NCX is expected when SR function is impaired, few and contradictory studies have addressed whether there is an absolute increase in NCX activity. The present study examines in detail NCX density and function in left ventricular midmyocardial myocytes isolated from normal or tachycardic pacing-induced failing canine hearts. No change of NCX current density was evident in myocytes from failing hearts when intracellular Ca(2+) (Ca(2+)) was buffered to 200 nmol/L. However, when Ca(2+) was minimally buffered with 50 micromol/L indo-1, Ca(2+) extrusion via NCX during caffeine application was doubled in failing versus normal cells. In other voltage-clamp experiments in which SR uptake was blocked with thapsigargin, both reverse-mode and forward-mode NCX currents and Ca(2+) transport were increased >2-fold in failing cells. These results suggest that, in addition to a relative increase in NCX function as a consequence of defective SR Ca(2+) uptake, there is an absolute increase in NCX function that depends on Ca(2+) in the failing heart.
心力衰竭中兴奋-收缩偶联缺陷通常与肌浆网（SR）钙摄取减少以及对经肌膜钠-钙交换（NCX）进行钙清除的更大依赖性有关。尽管当SR功能受损时预计NCX会相对增加，但很少有研究且结果相互矛盾，探讨NCX活性是否有绝对增加。本研究详细检测了从正常或快速起搏诱导的衰竭犬心脏分离的左心室中层心肌细胞中的NCX密度和功能。当细胞内钙（[Ca²⁺]i）缓冲至200 nmol/L时，衰竭心脏的心肌细胞中NCX电流密度无明显变化。然而，当用50 μmol/L吲哚-1对[Ca²⁺]i进行最小程度缓冲时，与正常细胞相比，应用咖啡因期间通过NCX的钙外排在衰竭细胞中增加了一倍。在其他电压钳实验中，用毒胡萝卜素阻断SR摄取时，衰竭细胞中的反向模式和正向模式NCX电流以及钙转运均增加了2倍以上。这些结果表明，除了由于SR钙摄取缺陷导致NCX功能相对增加外，衰竭心脏中NCX功能还有绝对增加，且这种增加依赖于[Ca²⁺]i 。
