A CA-DEPENDENT MODULATOR PROTEIN OF THE NA-K ATPASE

作者最近的工作表明，Na-K-ATPase的敏感性 而人红细胞的Na-K泵对钙的抑制作用是增加20 被存在于红细胞质中的一种未知蛋白质折叠。这个 蛋白质不是钙调蛋白，似乎与人红细胞膜结合 细胞内钙依赖，并增加Na-K的敏感性 ATPase在一定程度上，50%的抑制可以发生在低微摩尔 游离钙浓度。如果这种蛋白质也改变了钙对钙的影响 其他细胞中的Na-K-ATPase，那么它就可以在 Na-K泵在多种条件下的细胞调节。例如, 它可能参与了钠钾泵与血管紧张素转换酶之间的关系。 Na/Ca交换与心肌细胞内游离钙的调控 强心苷类药物的变力作用及其相互关系 钠代谢和高血压之间的关系。 被提议的项目的第一个目标是净化和识别 蛋白质；第二是测定其相对分子质量，氨基酸 组合物、末端和可能的假体基团。第三个目标 目的是研究纯化蛋白对钙离子抑制钠钾通道的影响。 人红细胞膜中的ATPase；四是建立其 对纯化的Na-K-ATPase的影响。第五个也是最后一个目标是 高血压病患者Na-K-ATPase的变化 对钙的抑制比正常情况更敏感，并确定其作用 纯化的蛋白质可能在这种差异中发挥作用。拟议的工作将 需要三年才能完成。

Recent work by the author has shown that the sensitivity of the Na-K ATPase and Na-K pump of human red blood cells to inhibition by Ca is increased 20 fold by an unidentified protein present in the cytoplasm of red cells. The protein is not calmodulin, appears to bind to the membrane of human red cells in a Ca-dependent manner, and increases the sensitivity of the Na-K ATPase to the extent that 50% inhibition can occur at low micromolar concentrations of free Ca. If this protein also alters the effect of Ca on the Na-K ATPase in other cells, then it could play a fundamental role in cellular regulation of the Na-K pump under many conditions. For instance, it could be involved in the relationship between the Na-K pump and the Na/Ca exchange and the control of free Ca in smooth muscle which may underlie the inotropic effect of cardiac glycosides and the relationship between sodium metabolism and hypertension. The first aim of the proposed project is to purify and identify the protein; the second is to determine its molecular weight, amino acid composition, end terminals, and possible prosthetic groups. The third aim is to study the effect of the purified protein on Ca inhibition of the Na-K ATPase in human red cell membranes and the fourth is to establish its effect on the purified Na-K ATPase. The fifth and final aim is to investigate if the Na-K ATPase in patients with essential hypertension are more sensitive than normal to inhibition by Ca and to establish what role the purified protein may play in such differences. The proposed work will require three years to complete.