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 was via ENaC, then amiloride, an ENaC inhibitor, should block AFC. But 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 non-selective for Na+ over K+, has a larger conductance, and shorter open and closed times. These two channel types are known as highly-selective channels (HSC) and non-selective 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 1 (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/dry ratio is increased, but the percentage increase in wet/dry ratio is larger than expected based on the reduction in AFC.
- Non-selective cation channels
- lung fluid balance
- Copyright © 2016, American Journal of Physiology-Lung Cellular and Molecular Physiology