期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 312, 期 6, 页码 L797-L811出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00379.2016
关键词
nonselective cation channels; acid-sensing ion channel 1a; alpha-epithelial Na+ channels; alveoli; lung fluid balance; alveolar fluid clearance
资金
- American Physiological Society
- National Institutes of Health [DK-37963, K12-GM-000680, T32-HL-076118, K01-DK-099617]
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 alpha-ENaC since knocking down alpha-ENaC reduces the number of NSC (knocking down beta- or gamma-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 alpha-ENaC and one or more acid-sensing ion channel 1a (ASIC1a) proteins. Knocking down either alpha-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据