ABNORMAL HEMOGLOBINS, CATIONS, AND VOLUME IN RED CELLS

拟议中的研究计划将重点放在突变之间的关系上 血红蛋白的一级结构和调节阳离子的机制 人红细胞的含量和细胞体积。 这一提议源于我们的 观察到CC细胞（血红蛋白C纯合细胞）具有 哇巴因-布美他尼耐药钾转运途径，即pH和体积 依赖性，并允许CC细胞在肿胀时调节其体积。 的 发生CC电池中描述的阳离子和水含量的减少 通过这条途径。 这表明，相对而言， 带正电的血红蛋白C参与激活参与的途径 细胞体积的控制。 具体目标包括：1）进一步表征pH和体积 CC细胞的依赖性K转运系统; 2）测试以下假设： 血红蛋白C负责激活该途径; 3） 其它相对正离子的阳离子输运性质研究 或带负电荷的血红蛋白变体; 4）检查 参与控制阳离子和水含量，以及细胞体积， 血红蛋白S和SC的纯合（SS）和杂合（AS）细胞 细胞及其在细胞镰状化中的作用。 这些研究应该提供新的信息的机制， CC细胞中K转运的pH和体积依赖性途径被激活。 此外，这些研究还可能为以下方面的作用提供新的见解： 血红蛋白-膜相互作用调节阳离子含量， 细胞体积，并可能提供一种新的方法来研究阳离子 镰状化引起的渗透性变化。

The proposed research plan will focus on the relationship between mutations in the primary structure of hemoglobin and mechanisms regulating cation content and cell volume of human red cells. This proposal stems from our observation that CC cells (cells homozygous for hemoglobin C) possess a ouabain- bumetanide-resistant pathway for K transport that is pH and volume dependent and allows CC cells to regulate their volume upon swelling. The reduction of cation and water content described in CC cells takes place through this pathway. This suggests a possible role for the relatively positive charged hemoglobin C in the activation of a pathway involved in the control of cell volume. Specific aims include: 1) Further characterization of the pH and volume dependent K transport system of CC cells; 2) Testing the hypothesis that hemoglobin C is responsible for the activation of this pathway; 3) Investigation of cation transport properties of other relatively positive or negative charged hemoglobin variants; 4) Examination of the mechanisms involved in the control of cation and water content, and cell volume in cells homozygous (SS), and heterozygous (AS) for hemoglobin S, and SC cells, and their role in cell sickling. These studies should provide new information on the mechanism by which this pH and volume dependent pathway for K transport is activated in CC cells. In addition, these studies may also provide new insights into the role of hemoglobin-membrane interactions in the regulation of cation content and cell volume and possibly provide a new approach to the study of cation permeability changes induced by sickling.