Spectrum of ion channels in alveolar epithelial cells: implications for alveolar fluid balance

The efficient transition from placental to atmospheric delivery of oxygen at birth is critically dependent on rapid reabsorption of fetal lung fluid. In the perinatal period, this process is driven by active transepithelial sodium transport and is almost exclusively dependent on expression and modulation of the amiloride-sensitive epithelial sodium channel (ENaC). However, later in development, the amiloride sensitivity of the reabsorptive response, which must be sustained to keep the lungs effectively dry, wanes as a function of postnatal age. This Featured Topic (Experimental Biology Meeting, Washington, DC, April, 2004) presented exciting new evidence to demonstrate that, in addition to ENaC, the adult alveolar epithelium expresses a plethora of amiloride-insensitive ion channels, including cystic fibrosis transmembrane conductance regulator, proton channels, voltage-dependent potassium channels, and cyclic nucleotide-gated cation channels. Furthermore, important evidence for selective modulation of ENaC subunits in the lung in response to cardiovascular disease was demonstrated. Finally, it is clear that newly emerging models of human alveolar epithelium in combination with the novel lung slice electrophysiological preparation will ensure that the ascription of function to specific ion channels in the in situ human lung will soon be a real possibility.