CFTR null mutation altered cAMP-sensitive and swelling-activated Cl- currents in primary cultures of mouse nephron.
The role of cystic fibrosis transmembrane conductance regulator (CFTR) in the control of Cl(-) currents was studied in mouse kidney. Whole cell clamp was used to analyze Cl(-) currents in primary cultures of proximal and distal convoluted and cortical collecting tubules from wild-type (WT) and cftr knockout (KO) mice. In WT mice, forskolin activated a linear Cl(-) current only in distal convoluted and cortical collecting tubule cells. This current was not recorded in KO mice. In both mice, Ca(2+)-dependent Cl(-) currents were recorded in all segments. In WT mice, volume-sensitive Cl(-) currents were implicated in regulatory volume decrease during hypotonicity. In KO mice, regulatory volume decrease and swelling-activated Cl(-) current were impaired but were restored by adenosine perfusion. Extracellular ATP also restored swelling-activated Cl(-) currents. The effect of ATP or adenosine was blocked by 8-cyclopentyl-1,3-diproxylxanthine. The ecto-ATPase inhibitor ARL-67156 inhibited the effect of hypotonicity and ATP. Finally, in KO mice, volume-sensitive Cl(-) currents are potentially functional, but the absence of CFTR precludes their activation by extracellular nucleosides. This observation strengthens the hypothesis that CFTR is a modulator of ATP release in epithelia.
Barrière
Hervé
H
Unité Mixte de Recherche Centre National de la Recherche Scientifique 6548, Université de Nice-Sophia Antipolis, 06108 Nice Cedex 2, France.
Belfodil
Radia
R
Rubera
Isabelle
I
Tauc
Michel
M
Poujeol
Chantal
C
Bidet
Michel
M
Poujeol
Philippe
P
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D018345:Mice, Knockout; D009154:Mutation; D009399:Nephrons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D014162:Transfection
D018118:Chloride Channels; D002712:Chlorides; D004791:Enzyme Inhibitors; D007038:Hypotonic Solutions; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium