CALMODULIN-ACTIVATED CA ATPASE IN PSYCHIATRIC ILLNESSES

细胞内钙离子作为第二信使 许多哺乳动物细胞，包括一些神经元，在正常情况下 极低的静息浓度会在反应中瞬间升高 对荷尔蒙、电或机械刺激。血浆 这些细胞的膜上含有一种酶系统，它 将多余的钙“泵”出细胞，从而恢复 休息状态，为下一个信号做准备。这种酶 该系统由膜结合的钙ATPase组成，该酶 当细胞内的钙离子被可溶性钙调蛋白激活时 浓度会增加。因为相同的酶系统存在于 人的红细胞膜，它可以方便地在 为临床目的采集的血液样本。 应用一种敏感而困难的技术，称为 “动力学滴定”，产生三个独立的参数 确定这个酶系统的特征。这些是：实力 钙调素与酶的结合，膜浓度 与钙调蛋白结合的酶的最大速度 钙调蛋白激活系统。到目前为止，结果表明 正常人与双相情感障碍患者在以下方面的差异 其中一些参数。参数值也非常具有 情绪和诊断类别的变化。所有这些方面的方向 这些变化表明，成功的治疗在 周期的抑郁结束与更有效的 钙泵。这是本研究的具体目的在于探索 这些观察更详细；长期目标是 对细胞内的作用有更深入的了解 精神疾病中的钙。

Intracellular ionized calcium serves as a second messenger for many mammalian cells, including some neurons, when its normally very low resting concentration is transiently elevated in response to hormonal, electrical, or mechanical stimuli. The plasma membrane of these cells contains an enzyme system which "pumps" the excess calcium out of the cells, thus restoring the resting condition in preparation for the next signal. This enzyme system consists of a membrane-bound calcium ATPase which is activated by soluble calmodulin in the cell when the calcium concentration increases. Since the same enzyme system exists in membranes of human erythrocytes, it is studied conveniently in blood samples which had been obtained for clinical purposes. Application of a sensitive and difficult technique, termed a "kinetic titration", yields three independent parameters which characterize this enzyme system. These are: the strength of binding of calmodulin to the enzyme, the membrane concentration of the enzyme that binds calmodulin, and the maximal velocity of the calmodulin-activated system. The results to date show clear differences between normals and bipolar patients with respect to some of these parameters. Parameter values also very with changes in mood and diagnostic category. The direction of all of these changes is such as to suggest that successful therapy during the depressive end of the cycle is associated with more effective calcium pumping. It is the specific aim of this study to explore these observations in more detail; the long term goal is directed toward an enlarged understanding of the role of intracellar calcium in mental illness.