K-DEPENDENT NA/CA EXCHANGE IN HUMAN PLATELETS

最近的工作表明，血小板Na/Ca交换器（NCX）在人类是相同的视网膜杆NCX。 该交换器在调节血小板Ca储存中起重要作用，并且它不仅由Na电化学梯度驱动，而且由穿过血小板质膜的K电化学梯度驱动。 此外，血小板表达钠泵的α 3亚型，这是一种对强心苷敏感性提高的亚型。 血小板离子转运的这些特征强烈地将血小板Ca代谢与全身Na和K稳态的波动以及血小板Na泵的活性联系起来。 该项目的核心是假设血小板Ca稳态和全身Na/K调节之间的联系解释了高Na和高K摄入的一些心血管效应，这些效应独立于Na和K摄入对血压的影响。 三个具体目标将探讨这一假设。 具体目标1将破译人类血小板中钠泵的生理和分子特征，重点是这些细胞中的α 3亚基亚型及其对强心苷的敏感性。 结果将提供一个更好的评价之间的联系血小板NCX和钠泵。 具体目标2将检验以下假设：高Na摄入量升高细胞溶质Na，降低细胞溶质K，并抑制NCX以增加人类血小板Ca储存和血小板反应性。 具体目标3将检验以下假设：高钾摄入量降低细胞溶质Na，升高细胞溶质K，刺激血小板NCX活性，以减少人类血小板Ca储存和血小板反应性。该项目的研究结果可能会发现以前未知的饮食钠和钾对心血管的影响，从而揭示人类“盐敏感性”的新维度。

Recent work has demonstrated that the platelet Na/Ca exchanger (NCX) in human beings is identical to the retinal rod NCX. This exchanger plays an important role in regulating platelet Ca stores and it is driven not only by the Na electrochemical gradient but also by the K electrochemical gradient across the platelet plasma membrane. In addition, platelets express the alpha3 isoform of the Na-pump, an isoform with a heightened sensitivity to cardiac glycosides. These features of the platelet ion transport strongly link platelet Ca metabolism to fluctuations in systemic Na and K homeostasis and to the activity of the platelet Na-pump. At the core of this project is the hypothesis that the link between platelet Ca homeostasis and systemic Na/K regulation explains some cardiovascular effects of high Na and high K intakes that are independent of the effects of Na and K intakes on blood pressure. Three specific aims will explore this hypothesis. Specific Aim 1 will decipher the physiological and molecular characteristics of the Na-pump in human platelets, focusing on the alpha3 subunit isoform in these cells and its sensitivity to cardiac glycosides. The results will provide a better appreciation of the link between platelet NCX and the Na-pump. Specific Aim 2 will test the hypothesis that a high Na intake raises cytosolic Na, lowers cytosolic K, and inhibits the NCX to increase platelet Ca stores and platelet reactivity in human beings. Specific Aim 3 will test the hypothesis that a high K intake lowers cytosolic Na, raises cytosolic K and stimulates platelet NCX activity to diminish platelet Ca stores and platelet reactivity in human beings. Findings of this project might identify previously unknown cardiovascular effects of dietary Na and K, thereby revealing a new dimension of 'salt sensitivity' in human beings.