Regulation of Na+ Channels in Lung Alveolar Type II Epithelial Cells

Abstract

Amiloride-sensitive sodium channels in the lung play an important role in lung fluid balance. Particularly in the alveoli, sodium transport is closely regulated to maintain an appropriate fluid layer on the surface of the alveoli. Alveolar type II cells appear to play an important role in this sodium transport. In alveolar type II cells, there are a variety of different amiloride-sensitive, sodium-permeable channels. This significant diversity appears to play a role in both normal lung physiology and pathologic states. In many epithelial tissues, amiloride-sensitive epithelial sodium channels (ENaC) are formed from three subunit proteins designated alpha-ENaC, beta-ENaC, and gamma-ENaC. At least part of the diversity of sodium-permeable channels in lung arises from assembling different combinations of these subunits to form channels with different biophysical properties and different mechanisms for regulation. This leads to epithelial tissue in the lung that has enormous flexibility to alter the magnitude and regulation of salt and water transport. In this article, we discuss the regulation of ENaCs composed of varying subunits and some of the implications of the regulation for normal pulmonary function.

Cholinergic regulation of epithelial sodium channels in rat alveolar type 2 epithelial cells

“…Y-27632 gradually reduced ENaC activity over a 25-min period after application. Addition of forskolin (10 M), which normally strongly activates ENaC (3,5,6,17,18), failed to increase channel activity. Thus RhoA appeared to be an essential factor for ENaC activity.…”

Novel and Extensive Aspects of Paraquat-Induced Pulmonary Fibrogenesis: Comparative and Time-Course Microarray Analyses in Fibrogenic and Non-Fibrogenic Rats

“…PQ uptake is significantly prevented when extracellular sodium is reduced (Dinis-Oliveira et al, 2006). The amiloride-sensitive cation channel is a major sodium channel, and Na + /K + -ATPase is important for its activation (Dada and Sznajder, 2003;Eaton et al, 2004;Egli et al, 2004;Folkesson and Matthay, 2006;Kemp and Kim, 2004;Planès, et al, 2005;Matalon et al, 2002), as are potassium channels (O'Grady and Lee, 2003). The gene expression alterations of the Na + /Cl − -dependent neurotransmitter transporter gene, Slc17a1, Kcne1, Kcna1, Kcna4, Scn4a, Scn2b, Atp1a2, Accn2, and Accn3 could indicate changes in these functions.…”

Expression and function of the epithelial sodium channel δ-subunit in human respiratory epithelial cells in vitro

“…Highly selective sodium channels (HSC), with a large selectivity for sodium over potassium, poorly selective channels displaying moderate selectivity as well as the non-selective cation channels (NSC) have been defined in the alveolar epithelial cells by single channel measurements and are responsible for the alveolar transepithelial sodium transport [17]. While the classic αβγ-ENaC is believed to represent the HSC, the molecular basis of the two other groups has remained controversial, with homomeric α-ENaC channels, αβ-or αγ-ENaC channels as well as different combinations of subunits with δ-ENaC being the potential candidates [17,27]. Distinct affinities to the ENaC blocker amiloride also account for biophysical differences between the different channel types.…”