Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4
Physiological roles of the intermediate conductance, Ca2+-activated potassium channel Kcnn4
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DOI：
10.1074/jbc.m409627200
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发表时间：
2004-11-12
影响因子：
4.8
通讯作者：
Melvin, JE
中科院分区：
文献类型：
--
作者：
Begenisich, T;Nakamoto, T;Melvin, JE
三大类钙激活钾通道由其各自的单通道电导定义，即小、中和大电导通道，通常分别称为SK、IK和BK通道。SK通道可能由三个基因Kcnn 1 - 3编码，而IK和大多数BK通道最有可能分别是Kcnn 4和Slo（Kcnma 1）基因的产物。IK通道在造血系统的细胞和参与盐和流体运输的器官（包括结肠、肺和唾液腺）中显著表达。IK通道可能是红细胞中K+渗透性的基础，其与水分损失相关，这是镰状细胞病的病理生理学中的一个促成因素。IK通道也参与T淋巴细胞的活化。腮腺分泌液体的腺泡细胞同时表达IK和BK通道，这引起了人们对它们各自作用的质疑。为了测试由Kcnn 4基因编码的通道的生理作用，我们构建了其表达缺陷的小鼠。Kcnn 4基因敲除小鼠外观正常，生育能力正常，腮腺腺泡细胞不表达IK通道，红细胞丧失K+通透性。Kcnn 4基因敲除小鼠T淋巴细胞和红细胞的体积调节严重受损，但腮腺腺泡细胞正常。尽管失去了IK通道，腮腺的激活液体分泌是正常的。这些结果证实了红细胞、T淋巴细胞和腮腺腺泡细胞中的IK通道确实由Kcnn 4基因编码。这些通道在水运动和随后的红细胞和T淋巴细胞体积变化中的作用也得到了证实。令人惊讶的是，Kcnn 4通道似乎在腮腺中的液体分泌和调节体积减小中不起所需的作用。
Three broad classes of Ca2+-activated potassium channels are defined by their respective single channel conductances, i.e. the small, intermediate, and large conductance channels, often termed the SK, IK, and BK channels, respectively. SK channels are likely encoded by three genes, Kcnn1- 3, whereas IK and most BK channels are most likely products of the Kcnn4 and Slo (Kcnma1) genes, respectively. IK channels are prominently expressed in cells of the hematopoietic system and in organs involved in salt and fluid transport, including the colon, lung, and salivary glands. IK channels likely underlie the K+ permeability in red blood cells that is associated with water loss, which is a contributing factor in the pathophysiology of sickle cell disease. IK channels are also involved in the activation of T lymphocytes. The fluid-secreting acinar cells of the parotid gland express both IK and BK channels, raising questions about their particular respective roles. To test the physiological roles of channels encoded by the Kcnn4 gene, we constructed a mouse deficient in its expression. Kcnn4 null mice were of normal appearance and fertility, their parotid acinar cells expressed no IK channels, and their red blood cells lost K+ permeability. The volume regulation of T lymphocytes and erythrocytes was severely impaired in Kcnn4 null mice but was normal in parotid acinar cells. Despite the loss of IK channels, activated fluid secretion from parotid glands was normal. These results confirm that IK channels in red blood cells, T lymphocytes, and parotid acinar cells are indeed encoded by the Kcnn4 gene. The role of these channels in water movement and the subsequent volume changes in red blood cells and T lymphocytes is also confirmed. Surprisingly, Kcnn4 channels appear to play no required role in fluid secretion and regulatory volume decrease in the parotid gland.