Characteristics of Cl- uptake in rat alveolar type I cells.
Although Cl- transport in fetal lung is important for fluid secretion and normal lung development, the role of Cl- transport in adult lung is not well understood. In physiological studies, the cystic fibrosis transmembrane regulator (CFTR) plays a role in fluid absorption in the distal air spaces of adult lung, and alveolar type II cells cultured for 5 days have the capacity to transport Cl-. Although both alveolar type I and type II cells express CFTR, it has previously not been known whether type I cells transport Cl-. We studied Cl- uptake in isolated type I cells directly, using either radioisotopic tracers or halide-sensitive fluorescent indicators. By both methods, type I cells take up Cl-. In the presence of beta-adrenergic agonist stimulation, Cl- uptake can be inhibited by CFTR antagonists. Type I cells express both the Cl-/HCO3- anion exchanger AE2 and the voltage-gated Cl- channels CLC5 and CLC2. Inhibitors of AE2 also block Cl- uptake in type I cells. Together, these results demonstrate that type I cells are capable of Cl- uptake and suggest that the effects seen in whole lung studies establishing the importance of Cl- movement in alveolar fluid clearance may be, in part, the result of Cl- transport across type I cells.
Johnson
Meshell
M
Department of Medicine, University of California, San Francisco, 3333 California St., Suite 150, Box 1245, San Francisco, CA 94118, USA. meshell.johnson@ucsf.edu
Allen
Lennell
L
Dobbs
Leland
L
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D017920:Antiporters / Q000235:genetics / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D009579:Nitrobenzoates / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology*; D011806:Quinolinium Compounds / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D064606:SLC4A Proteins; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D027321:Anion Transport Proteins; D017920:Antiporters; D002712:Chlorides; D009579:Nitrobenzoates; D011806:Quinolinium Compounds; D012333:RNA, Messenger; D011868:Radioisotopes; D064606:SLC4A Proteins; D002034:Bumetanide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C085493:N-(ethoxycarbonylmethyl)-6-methoxyquinolinium; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000584:Amiloride; D013726:Terbutaline; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
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