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

Hervé Barrière (1) , Radia Belfodil (1) , Isabelle Rubera (1) , Michel Tauc (1) , Chantal Poujeol (1) , Michel Bidet (1, 2) , Philippe Poujeol (1)

1 PCMSI - Physiologie cellulaire et moléculaire des systèmes intégrés
2 ISP - Institut des Sciences sociales du Politique

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.

Domaines: Physiologie [q-bio.TO]

Hervé Barrière, Radia Belfodil, Isabelle Rubera, Michel Tauc, Chantal Poujeol, et al.. CFTR null mutation altered cAMP-sensitive and swelling-activated Cl- currents in primary cultures of mouse nephron.. AJP Renal Physiology, 2003, 284 (4), pp.F796-811. ⟨10.1152/ajprenal.00237.2002⟩. ⟨hal-00320822⟩