THE LUNG AMILORIDE-SENSITIVE NA- BIOPHYSICAL PROPERTIES, PHARMACOLOGY, ONTOGENY, AND MOLECULAR-CLONING( CHANNEL )

Water balance in the lung is controlled via active Na+ and Cl- transpo rt. Electrophysiological measurements on lung epithelial cells demonst rated the presence of a Na+ channel that is inhibited by amiloride (K0 .5 = 90 nM) and some of its derivatives such as phenamil (K0.5 = 19 nM ) and benzamil (K0.5 = 14 nM) but not by ethylisopropylamiloride. An a miloride-sensitive Na+ channel of 4 pS was recorded from outside-out p atches excised from the apical membrane. This channel is highly select ive for Na+ (P(Na+)/P(K+) greater-than-or-equal-to 10). Isolation of a human lung cDNA led to the primary structure of the lung Na+ channel. The corresponding protein is 669 residues long and has two large hydr ophobic domains. An amiloride-sensitive Na+-selective current apparent ly identical to the one observed in lung epithelial cells was recorded after expression of the cloned channel in oocytes. The level of the m RNA for the Na+ channel was highly increased from fetal to newborn and adult stages. This observation indicates that the increased Na+ reabs orption that occurs at birth as a necessary event to pass to an air-br eathing environment is probably associated with control of transcripti on of this Na+ channel. The human gene for the lung Na+ channel was ma pped on chromosome 12p13.