CFTR-Mediated anion conductance regulates Na(+)-K(+)-pump activity in Calu-3 human airway cells.
We studied the role of CFTR in the Na(+)-K(+)-pump activity of Calu-3 human airway cells. To estimate the Na(+)-K(+)-pump activity on the basolateral membrane, the ouabain-sensitive component of the short-circuit current (Isc) was measured after permeabilization of the apical membrane with nystatin, a Na(+) ionophore. The Na(+)-K(+)-pump activity was diminished by a selective CFTR blocker (glybenclamide) or nonspecific Cl(-) channel inhibitors (NPPB and DPC) but not by outwardly rectifying Cl(-) channel blockers (DNDS, DIDS). Augmentation of anion conductance by 8-bromo-cyclic AMP (8Br-cAMP, 1 mM) potentiated the Na(+)-K(+)-pump activity that was reduced by blocking CFTR or by the replacement of Cl(-) with gluconate, a less membrane-permeant anion. The Na(+)-K(+)-pump activity was unaffected by the replacement of Cl(-) with NO(-)(3) that has equal permeability through the CFTR. These results suggest that the anion movement through the CFTR may contribute to the Na(+)-K(+)-pump activity in Calu-3 cells by regulating the rate of Na(+) entry.
Ito
Y
Y
Second Division (Respiratory Division), Second Department of Internal Medicine, School of Medicine, Nagoya University, Tsurumai-cho, Showa-ku, Nagoya, 466, Japan. itoyasu@tsuru.med.nagoya-u.ac.jp
Mizuno
Y
Y
Aoyama
M
M
Kume
H
H
Yamaki
K
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000838:Anions / Q000378:metabolism*; D001980:Bronchi / Q000166:cytology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D013997:Time Factors; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000838:Anions; C505032:CFTR protein, human; D002121:Calcium Channel Blockers; D007476:Ionophores; D009579:Nitrobenzoates; D013267:Stilbenes; D062367:ortho-Aminobenzoates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D009761:Nystatin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D010042:Ouabain; C022306:4,4'-dinitro-2,2'-stilbenedisulfonic acid; C001209:fenamic acid; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005905:Glyburide