Modulation of lung epithelial ion channel activity by reactive oxygen nitrogen intermediates

Alveolar epithelial cells of mammalian lungs actively transport sodium (Na⁺) and chloride (Cl^-) ions and these processes are important in fluid homeostasis.  Sodium ions enter the apical membranes of both type I and type II alveolar epithelial cells through sodium selective, cation and cyclic nucleotide gated ion channels and are extruded across the basolateral membrane by the ouabain-sensitive Na,K-ATPase.  This vectorial transport of Na⁺ ions (and concomitant movement of Cl^- ions to maintain electroneutrality) creates an oncotic force leading to the reabsorption of fluid across both normal and damaged lungs. Nitric oxide and reactive oxygen nitrogen intermediates (formed by the reactions of nitric oxide with partially reduced oxygen species), generated in close proximity of epithelial cell membranes by activated inflammatory cells, modulate the activity of sodium channels via signal transduction mechanisms (such as activating PKG and PKC) or by post-translational oxidative modifications of sodium channel proteins and their chaperons. Channel activity (and vectorial sodium transport) may be either increased or decreased depending on levels of reactive intermediates and length of exposure. 

Reviews on this topic

Song W, Matalon S. Modulation of alveolar fluid clearance by reactive oxygen-nitrogen intermediates.  Am J Physiol Lung Cell Mol Physiol. 2007 Oct;293(4):L855-8. Epub 2007 Aug 10. Review.

Eaton DC, Chen J, Ramosevac S, Matalon S, Jain L. Regulation of Na⁺ channels in lung alveolar type II epithelial cells. Proc Am Thorac Soc. 2004;1(1):10-6. Review

Matalon S, O'Brodovich H.  Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance.  Annu Rev Physiol. 1999;61:627-61. Review.