title: Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats.
abstract: We investigated the cellular and molecular events associated with the increase in sodium transport across the alveolar epithelium of rats exposed to hyperoxia (85% O2 for 7 days followed by 100% O2 for 4 days). Alveolar type II (ATII) cell RNA was isolated and probed with a cDNA for one of the rat colonic epithelial sodium channel subunits (alpha rENaC). The alpha rENaC mRNA (3.7-kb transcript) increased 3-fold in ATII cell RNA isolated from rats exposed to 85% O2 for 7 days and 6-fold after 4 days of subsequent exposure to 100% O2. In situ hybridization revealed increased expression of alpha rENaC mRNA transcripts in both airway and alveolar epithelial cells of hyperoxic rats. When immunostained with a polyclonal antibody to kidney sodium channel protein, ATII cells from hyperoxic rats exhibited a significant increase in the amount of immunogenic protein present in both the plasma membrane and the cytoplasm. When patched in the whole-cell mode, ATII cells from hyperoxic rats exhibited amiloride and 5-(N-ethyl-N-isopropyl)-2',4'-amiloride (EIPA)-sensitive currents that were 100% higher compared with those obtained from air-breathing rats. Single-channel sodium currents (mean conductance of 25 pS) were seen in ATII cells patched in both the inside-out and cell-attached modes. The number and open probability of these channels increased significantly during exposure to hyperoxia. Exposure to sublethal hyperoxia up-regulated both alpha rENaC mRNA and the functional expression of sodium channels in ATII cells.
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham 35233-6810, USA.
authors.forename: G
authors.initials: G
authors.lastname: Yue
authors.forename: W J
authors.initials: WJ
authors.lastname: Russell
authors.forename: D J
authors.initials: DJ
authors.lastname: Benos
authors.forename: R M
authors.initials: RM
authors.lastname: Jackson
authors.forename: M A
authors.initials: MA
authors.lastname: Olman
authors.forename: S
authors.initials: S
authors.lastname: Matalon
mesh_terms: D000818:Animals; D001834:Body Water; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D015222:Sodium Channels