Lu Fang-Min, Deisl Christine, Hilgemann Donald W
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, United States.
Elife. 2016 Sep 14;5:e19267. doi: 10.7554/eLife.19267.
Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes.
钠钾泵活性的微小变化通过钠钙交换调节心肌细胞内的钙释放。我们现在反过来表明，细胞质钙的短暂升高强烈调节心脏钠钾泵。当细胞质钠处于次最大水平时，在细胞外施加钾期间，钠钾泵电流迅速衰减，多种结果表明涉及一种失活机制。通过反向钠钙交换短暂激活钙内流可增强泵电流并减弱电流衰减，而反复的钙升高则抑制泵电流。泵电流增强在3分钟内逆转，并且在缺乏调节蛋白磷膜蛋白的心肌细胞中结果相似。显然不涉及经典的信号传导机制，包括钙激活的蛋白激酶和活性氧。由疏水性离子（如己基三苯基鏻，C6TPP）的膜内运动介导的电信号与泵电流平行增加和减少。因此，钙的短暂升高和钠钾泵的失活会导致相反的肌膜变化，这可能会影响多种膜过程。
