Ion Channels: An Overview

Abstract

Efficient gas exchange in the lungs depends on precise regulation of the amount of fluid in the thin liquid layer lining the alveolar epithelium. Studies in vivo and in isolated lungs have shown that fluid can be transported from the alveolar into the interstitial spaces, and that this process can be partially inhibited by the addition of amiloride, a Na+ channel inhibitor, to the alveolar space. These results suggested that alveolar epithelial cells are the major sites of Na+ transport and fluid absorption in the adult lung. The alveolar epithelium, which covers more than 99% of the large internal surface area of the lung (~100–150m2 in humans), is composed of two distinct cell types, alveolar type I (AT1) and type II (AT2) cells. AT2 cells, which cover only 2–5% of the internal surface area of the lung, are cuboidal cells that secrete pulmonary surfactant. AT2 cells contain ion channels, including several forms of the amiloride-sensitive epithelial sodium channel, ENaC, and a chloride channel, the cystic fibrosis transmembrane regulator (CFTR). TI cells are large squamous cells whose thin cytoplasmic extensions cover >95% of the internal surface area of the lung. AT1 cells contain functional ENaC, pimozide-sensitive, cyclic nucleotide-gated, non-selective cation channels, and K+ channels, but do not appear to contain CFTR. Besides these ion channels, the apical membrane of most airway epithelia contains several members of the TRP family of calcium channels and several other types of Cl− channels. The Ca2+-activated Cl-channel (CLCA) is another anion channel at the apical membrane of airway epithelia that responds acutely to increases in intracellular calcium and is involved in transepithelial fluid transport. In some airway cells, there are also volume regulated Cl-channels (ClC family of channels) that respond to changes in cell volume to alter chloride transport.