ABNORMAL HEMOGLOBINS, CATIONS, AND VOLUME IN RED CELLS

拟议的研究计划将重点放在突变之间的关系上 在血红蛋白的一级结构和阳离子调节机制中 人红细胞的含量和细胞体积。这项建议源于我们的 观察到CC细胞(血红蛋白C纯合子细胞)具有 哇巴因-布美他尼抵抗钾转运的途径，即pH和体积 依赖，并允许CC细胞在肿胀时调节其体积。这个 在CC电池中描述的阳离子和水含量的减少发生 通过这条路。这表明，相对的 正电荷型血红蛋白C激活途径中的一条参与 细胞体积的控制。 具体目标包括：1)进一步表征pH值和体积 CC细胞依赖的钾转运系统；2)检验假设 血红蛋白C负责激活这一途径；3) 其他相对正离子的阳离子输运性质的研究 或带负电荷的血红蛋白变体；4)机制的检查 参与阳离子和水分含量的控制，以及细胞体积 细胞纯合子(SS)和杂合子(AS)的血红蛋白S，和SC 细胞，以及它们在细胞镰状中的作用。 这些研究应该提供关于这一机制的新信息 在CC细胞中，pH和体积依赖的钾转运通路被激活。 此外，这些研究还可能为我们提供对 血红蛋白-膜相互作用在阳离子含量调节中的作用 细胞体积，为阳离子的研究提供了一种新的途径 镰刀引起的通透性变化。

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.