Amiloride-sensitive Na+ channels in human nasal epithelium are different from classical epithelial Na+ channels.
We characterized Na+ absorption in confluent monolayers of primary cultured epithelia derived from human nasal cystic fibrosis (CF) and non-CF epithelium in modified Ussing chambers. Amiloride-sensitive Na+ channels in cells obtained from CF as well as from non-CF patients showed properties different from all previously described epithelial Na+ channels (ENaC). DPC, a potent Cl- channel blocker, which has never been described to block ENaC, inhibited a considerable portion of the amiloride-sensitive Na+ absorption. In contrast to classical ENaC, cAMP induced no activation of amiloride-sensitive short-circuit current. Aldosterone failed to induce any functional stimulation of Na+ absorption in vitro when applied to the cell culture medium prior to measurements. Together with the reportedly reversible inhibition by phenamil we propose that Na+ absorption in human nasal epithelia is either regulated differently or is mediated by a yet still unknown member of the ENaC superfamily.
Rückes
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C
CF Working Group Giessen, Justus-Liebig-University, Germany.
Blank
U
U
Möller
K
K
Rieboldt
J
J
Lindemann
H
H
Münker
G
G
Clauss
W
W
Weber
W M
WM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D007700:Kinetics; D009297:Nasal Mucosa / Q000502:physiology* / Q000503:physiopathology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012016:Reference Values; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C505032:CFTR protein, human; D000644:Quaternary Ammonium Compounds; D015222:Sodium Channels; D062367:ortho-Aminobenzoates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; C001209:fenamic acid; D000242:Cyclic AMP; C027917:tetramethylammonium; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D015056:1-Methyl-3-isobutylxanthine