Reinecke H, Studer R, Vetter R, Holtz J, Drexler H
Universitatsklinik Freiburg, Kardiologie und Angiologie, Germany.
Cardiovasc Res. 1996 Jan;31(1):48-54.
The aim of the present study was to investigate the functional activity and expression of the sarcolemmal Na+/Ca2+-exchanger in the failing human heart.
Left ventricular samples were taken from eleven patients with end-stage heart failure and six organ donors (normal controls). The Na+/Ca2+-exchanger activity was assessed by measuring Na+ gradient-induced 45Ca2+ transport into sarcolemmal vesicles of quantitatively collected crude membrane preparations. The abundance of the Na+/Ca2+-exchanger protein was determined by Western blot analysis using a specific antiserum and the results were normalized to myocyte specific beta-myosin heavy chain protein content.
In membrane preparations of failing human hearts, both the Na+ gradient-induced 45Ca2+ transport activity and the level of immunoreactive Na+/Ca2+-exchanger protein were increased (P < 0.01) by 87% and 160% compared to controls, respectively.
In human end-stage heart failure the increased sarcolemmal Na+/Ca2+-exchanger activity appears to be due to an elevated expression of this protein. An increase in the expression and activity of the Na+/Ca2+-exchanger in the failing human heart may be of important functional significance: while a resulting increase in Ca2+ extrusion across the sarcolemma may limit diastolic Ca2+ overload, a corresponding influx of Na+ may be associated with membrane depolarization and enhanced arrhythmogenesis if the Na+/Ca2+-exchanger operates primarily in the forward mode.
本研究旨在调查衰竭的人类心脏中肌膜钠/钙交换体的功能活性及表达情况。
从11例终末期心力衰竭患者及6例器官捐献者（正常对照）获取左心室样本。通过测量钠梯度诱导的45钙转运进入定量收集的粗制膜制剂的肌膜囊泡来评估钠/钙交换体活性。使用特异性抗血清通过蛋白质印迹分析确定钠/钙交换体蛋白的丰度，并将结果标准化为心肌特异性β-肌球蛋白重链蛋白含量。
与对照组相比，在衰竭的人类心脏的膜制剂中，钠梯度诱导的45钙转运活性及免疫反应性钠/钙交换体蛋白水平分别增加了87%和160%（P<0.01）。
在人类终末期心力衰竭中，肌膜钠/钙交换体活性增加似乎是由于该蛋白表达升高所致。衰竭的人类心脏中钠/钙交换体表达和活性的增加可能具有重要的功能意义：虽然肌膜上钙外流增加可能限制舒张期钙超载，但如果钠/钙交换体主要以前向模式运作，相应的钠内流可能与膜去极化及心律失常增加有关。
