CFTR null mutation altered cAMP-sensitive and swelling-activated Cl- currents in primary cultures of mouse nephron

被引:32
作者
Barrière, H [1 ]
Belfodil, R [1 ]
Rubera, I [1 ]
Tauc, M [1 ]
Poujeol, C [1 ]
Bidet, M [1 ]
Poujeol, P [1 ]
机构
[1] Univ Nice Sophia Antipolis, CNRS, UMR 6548, F-06108 Nice 2, France
关键词
kidney; cystic fibrosis; cell volume; regulatory volume decrease;
D O I
10.1152/ajprenal.00237.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:F796 / F811
页数:16
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