CFTR-dependent and -independent swelling-activated K+ currents in primary cultures of mouse nephron.
The role of CFTR in the control of K(+) currents was studied in mouse kidney. Whole cell clamp was used to identify K(+) currents on the basis of pharmacological sensitivities in primary cultures of proximal (PCT) and distal convoluted tubule (DCT) and cortical collecting tubule (CCT) from wild-type (WT) and CFTR knockout (KO) mice. In DCT and CCT cells, forskolin activated a 293B-sensitive K(+) current in WT, but not in KO, mice. In these cells, a hypotonic shock induced K(+) currents blocked by charybdotoxin in WT, but not in KO, mice. In PCT cells from WT and KO mice, the hypotonicity-induced K(+) currents were insensitive to these toxins and were activated at extracellular pH 8.0 and inhibited at pH 6.0, suggesting that the corresponding channel was TASK2. In conclusion, CFTR is implicated in the control of KCNQ1 and Ca(2+)-sensitive swelling-activated K(+) conductances in DCT and CCT, but not in proximal convoluted tubule, cells. In KO mice, impairment of the regulatory volume decrease process in DCT and CCT could be due to the loss of an autocrine mechanism, implicating ATP and adenosine, which controls swelling-activated Cl(-) and K(+) channels.
Belfodil
Radia
R
Unité Mixte de Recherche Centre National de la Recherche Scientifique 6548 Université de Nice-Sophia Antipolis, O6108 Nice Cedex 2, France.
Barrière
Hervé
H
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 / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018181:Mice, Inbred CFTR; D009399:Nephrons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D007038:Hypotonic Solutions; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000241:Adenosine; D011188:Potassium; D002118:Calcium