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首页> 美国卫生研究院文献>American Journal of Physiology - Lung Cellular and Molecular Physiology >Ion Channels and Transporters in Lung Function and Disease: Alveolar nonselective channels are ASIC1a/α-ENaC channels and contribute to AFC
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Ion Channels and Transporters in Lung Function and Disease: Alveolar nonselective channels are ASIC1a/α-ENaC channels and contribute to AFC

机译：肺功能和疾病中的离子通道和转运蛋白：肺泡非选择性通道是ASIC1a /α-ENaC通道有助于AFC

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摘要

A thin fluid layer in alveoli is normal and results from a balance of fluid entry and fluid uptake by transepithelial salt and water reabsorption. Conventional wisdom suggests the reabsorption is via epithelial Na+ channels (ENaC), but if all Na+ reabsorption were via ENaC, then amiloride, an ENaC inhibitor, should block alveolar fluid clearance (AFC). However, amiloride blocks only half of AFC. The reason for failure to block is clear from single-channel measurements from alveolar epithelial cells: ENaC channels are observed, but another channel is present at the same frequency that is nonselective for Na+ over K+, has a larger conductance, and has shorter open and closed times. These two channel types are known as highly selective channels (HSC) and nonselective cation channels (NSC). HSC channels are made up of three ENaC subunits since knocking down any of the subunits reduces HSC number. NSC channels contain α-ENaC since knocking down α-ENaC reduces the number of NSC (knocking down β- or γ-ENaC has no effect on NSC, but the molecular composition of NSC channels remains unclear). We show that NSC channels consist of at least one α-ENaC and one or more acid-sensing ion channel 1a (ASIC1a) proteins. Knocking down either α-ENaC or ASIC1a reduces both NSC and HSC number, and no NSC channels are observable in single-channel patches on lung slices from ASIC1a knockout mice. AFC is reduced in knockout mice, and wet wt-to-dry wt ratio is increased, but the percentage increase in wet wt-to-dry wt ratio is larger than expected based on the reduction in AFC.
机译：肺泡中薄薄的液体层是正常现象，其原因是上皮盐和水的重吸收可以平衡液体进入和液体吸收。传统观点认为，重吸收是通过上皮的Na + 通道（ENaC）进行的，但是，如果所有Na + 重吸收都是通过ENaC进行的，则ENaC抑制剂阿米洛利应该阻断肺泡液许可（AFC）。但是，阿米洛利仅阻断AFC的一半。从肺泡上皮细胞的单通道测量中可以清楚地知道阻止阻塞的原因：观察到ENaC通道，但是另一个通道以与Na + 相对于K 非选择性的相同频率存在+ ，具有更大的电导，并且打开和关闭时间更短。这两种通道类型称为高选择性通道（HSC）和非选择性阳离子通道（NSC）。 HSC通道由三个ENaC子单元组成，因为敲除任何一个亚单元都会减少HSC数量。 NSC通道包含α-ENaC，因为敲除α-ENaC会减少NSC的数量（敲除β-或γ-ENaC对NSC没有影响，但NSC通道的分子组成仍然不清楚）。我们显示NSC通道至少由一个α-ENaC和一个或多个酸敏感离子通道1a（ASIC1a）蛋白质组成。敲除α-ENaC或ASIC1a都会减少NSC和HSC的数目，在ASIC1a剔除小鼠的肺切片上的单通道斑块中没有NSC通道可观察到。基因敲除小鼠的AFC减少，湿重干重比增加，但湿重干重比的增加百分比大于基于AFC减少的预期。

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