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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells
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The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells

机译：hSK4（KCNN4）亚型是人类红细胞中的Ca2 +激活的K +通道（Gardos通道）

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摘要

The question is, does the isoform hSK4, also designated KCNN4, represent the small conductance, Ca2+-activated K+ channel (Gardos channel) in human red blood cells? We have analyzed human reticulocyte RNA by RT-PCR, and, of the four isoforms of SK channels known, only SK4 was found. Northern blot analysis of purified and synchronously growing human erythroid progenitor cells, differentiating from erythroblasts to reticulocytes, again showed only the presence of SK4. Western blot analysis, with an anti-SK4 antibody, showed that human erythroid progenitor cells and, importantly, mature human red blood cell ghost membranes, both expressed the SK4 protein. The Gardos channel is known to turn on, given inside Ca2+, in the presence but not the absence of external K-o(+) and remains refractory to K-o(+) added after exposure to inside Ca2+. Heterologously expressed SK4, but not SK3, also shows this behavior. In inside-out patches of red cell membranes, the open probability (P-o) of the Gardos channel is markedly reduced when the temperature is raised from 27 to 37degreesC. Net K+ efflux of intact red cells is also reduced by increasing temperature, as are the P-o values of inside-out patches of Chinese hamster ovary cells expressing SK4 (but not SK3). Thus the envelope of evidence indicates that SK4 is the gene that codes for the Gardos channel in human red blood cells. This channel is important pathophysiologically, because it represents the major pathway for cell shrinkage via KCl and water loss that occurs in sickle cell disease. [References: 42]
机译：问题是，同种型hSK4（也称为KCNN4）是否代表人红细胞中的小电导，Ca2 +激活的K +通道（Gardos通道）？我们已经通过RT-PCR分析了人类网织红细胞RNA，在已知的SK通道的四种同工型中，仅发现了SK4。纯化和同步生长的人红系祖细胞（从成红细胞到网状细胞的分化）的Northern印迹分析再次显示仅存在SK4。用抗SK4抗体进行的蛋白质印迹分析表明，人红系祖细胞，以及重要的是成熟的人红细胞鬼膜，均表达SK4蛋白。已知在存在Ca 2+的情况下打开Gardos通道，但存在外部K-o（+），但不存在外部K-o（+），并且在暴露于内部Ca2 +之后仍对添加的K-o（+）保持不溶。异源表达的SK4，但不是SK3，也显示了此行为。在红细胞膜由内而外的区域中，当温度从27摄氏度升高到37摄氏度时，加多斯通道的打开概率（P-o）显着降低。升高温度还会降低完整红细胞的净K +外流，表达SK4（但不包括SK3）的中国仓鼠卵巢细胞的内向外斑块的P-o值也会降低。因此，有证据表明SK4是编码人红细胞中Gardos通道的基因。该通道在病理生理上很重要，因为它代表镰状细胞疾病中发生的经由KCl和失水的细胞收缩的主要途径。 [参考：42]

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