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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system.
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A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system.

机译：导致Liddle病的上皮钠通道中的突变增加了非洲爪蟾卵母细胞表达系统中的通道活性。

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摘要

We have studied the functional consequences of a mutation in the epithelial Na+ channel that causes a heritable form of salt-sensitive hypertension, Liddle disease. This mutation, identified in the original kindred described by Liddle, introduces a premature stop codon in the channel beta subunit, resulting in a deletion of almost all of the C terminus of the encoded protein. Coexpression of the mutant beta subunit with wild-type alpha and gamma subunits in Xenopus laevis oocytes resulted in an approximately 3-fold increase in the macroscopic amiloride-sensitive Na+ current (INa) compared with the wild-type channel. This change in INa reflected an increase in the overall channel activity characterized by a higher number of active channels in membrane patches. The truncation mutation in the beta subunit of epithelial Na+ channel did not alter the biophysical and pharmacological properties of the channel--including unitary conductance, ion selectivity, or sensitivity to amiloride block. These results provide direct physiological evidence that Liddle disease is related to constitutive channel hyperactivity in the cell membrane. Deletions of the C-terminal end of the beta and gamma subunits of rat epithelial Na+ channel were functionally equivalent in increasing INa, suggesting that the cytoplasmic domain of the gamma subunit might be another molecular target for mutations responsible for salt-sensitive forms of hypertension.
机译：我们已经研究了上皮Na +通道突变的功能后果，该突变导致可遗传形式的盐敏感型高血压Liddle疾病。在Liddle最初描述的这种突变中发现了这种突变，它在通道β亚基中引入了一个过早的终止密码子，导致几乎所有编码蛋白的C末端都缺失了。与野生型通道相比，非洲爪蟾卵母细胞中突变型β亚基与野生型α和γ亚基的共表达导致宏观阿米洛利敏感Na +电流（INa）约增加了3倍。 INa的这种变化反映了总通道活性的增加，其特征是膜片中活性通道数量增加。上皮Na +通道β亚基的截短突变不会改变该通道的生物物理和药理特性-包括单位电导，离子选择性或对阿米洛利阻滞的敏感性。这些结果提供了直接的生理学证据，即Liddle病与细胞膜中的组成性通道过度活跃有关。大鼠上皮Na +通道的β和γ亚基的C末端的缺失在增加INa方面在功能上是等效的，这表明γ亚基的胞质域可能是引起盐敏感型高血压的另一种分子靶标。

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