Bookchin Robert M, Lew Virgilio L
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Curr Opin Hematol. 2002 Mar;9(2):107-10. doi: 10.1097/00062752-200203000-00004.
A critical link between the single molecular defect in sickle cell anemia and the extensive pathology of this disease is the reversible increase in red cell membrane permeability generated by hemoglobin S polymers in the deoxygenated state. This permeability, usually described as P (sickle), triggers a chain of events in which two constitutive transporters of the red cell membrane become activated-the recently cloned intermediate conductance, Ca 2+ -sensitive K channel, and the electroneutral K:Cl cotransporter-leading to sickle cell dehydration. This article reviews knowledge of the dehydration mechanism, stressing the marked heterogeneity of dehydration rates in sickle cell populations, and discusses recent contributions to understanding of the function and regulation of P (sickle), Ca 2+ -sensitive K channel, and K:Cl cotransporter, and of therapies targeted at these transporters.
镰状细胞贫血中的单分子缺陷与该疾病广泛病理之间的关键联系是，在脱氧状态下由血红蛋白S聚合物产生的红细胞膜通透性的可逆增加。这种通透性通常称为P（镰状），它引发了一系列事件，其中红细胞膜的两个组成型转运蛋白被激活——最近克隆的中等电导、Ca2+敏感钾通道和电中性K:Cl共转运体——导致镰状细胞脱水。本文回顾了脱水机制的相关知识，强调了镰状细胞群体中脱水速率的显著异质性，并讨论了最近在理解P（镰状）、Ca2+敏感钾通道和K:Cl共转运体的功能与调节以及针对这些转运体的治疗方法方面所取得的进展。
