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Role of TASK2 Potassium Channels Regarding Volume Regulation in Primary Cultures of Mouse Proximal Tubules

Herve Barriere¹, Radia Belfodil¹, Isabelle Rubera¹, Michel Tauc¹, Florian Lesage², Chantal Poujeol¹, Nicolas Guy², Jacques Barhanin² and Philippe Poujeol¹

¹ UMR Centre National de la Recherche Scientifique (CNRS) 6548, Université de Nice-Sophia Antipolis, 06108 Nice Cedex 2, France
² l'Institut de Pharmacologie Moléculaire et Cellulaire, UMR CNRS 6097, 06560 Valbonne Sophia Antipolis, France

Address correspondence to Dr. P. Poujeol, UMR CNRS 6548, Bâtiment Sciences Naturelles, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France. Fax: (33) 04 92 07 68 50; email: poujeol{at}unice.fr

Several papers reported the role of TASK2 channels in cell volume regulation and regulatory volume decrease (RVD). To check the possibility that the TASK2 channel modulates the RVD process in kidney, we performed primary cultures of proximal convoluted tubules (PCT) and distal convoluted tubules (DCT) from wild-type and TASK2 knockout (KO) mice. In KO mice, the TASK2 coding sequence was in part replaced by the lac-Z gene. This allows for the precise localization of TASK2 in kidney sections using ß-galactosidase staining. TASK2 was only localized in PCT cells. K⁺ currents were analyzed by the whole-cell clamp technique with 125 mM K-gluconate in the pipette and 140 mM Na-gluconate in the bath. In PCT cells from wild-type mice, hypotonicity induced swelling-activated K⁺ currents insensitive to 1 mM tetraethylammonium, 10 nM charybdotoxin, and 10 µM 293B, but blocked by 500 µM quinidine and 10 µM clofilium. These currents were increased in alkaline pH and decreased in acidic pH. In PCT cells from TASK2 KO, swelling-activated K⁺ currents were completely impaired. In conclusion, the TASK2 channel is expressed in kidney proximal cells and could be the swelling-activated K⁺ channel responsible for the cell volume regulation process during osmolyte absorptions in the proximal tubules.

Key Words: regulatory volume decrease • potassium conductance • two-pore K(⁺) channels • kidney • KCNK5

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