Submitted on April 18, 2006
Accepted on September 20, 2006
Extracellular pH alkalinisation by Cl-/HCO3- exchanger is crucial for TASK2 activation by hypotonic shock in proximal cell lines from mouse kidney
Sébastien L'Hoste1, Herve Barriere2, Radia Belfodil2, Isabelle Rubera2, Christophe Duranton2, Michel Tauc2, Chantal Poujeol2, Jacques Barhanin3, and Philippe Poujeol2*
1 biology, UMR CNRS 6548, Nice Cedex 2, France
2 biology, CNRS UMR 6548, Nice, France
3 CNRS Sophia-Antipolis, France, nice, France
* To whom correspondence should be addressed. E-mail: Philippe.poujeol{at}unice.fr.
We have previously shown that TASK2 channels and the swelling-activated Cl- currents are involved in regulatory volume decrease (RVD). The aim of this study was to determine the mechanism responsible for the activation of TASK2 channels during RVD. For this purpose, the effect of buffering capacity of external bath on K+ currents and relative cell volume were analysed. In presence of high buffer concentration (30 mM HEPES), the cells did not undergo RVD and did not develop outward K+ currents (TASK2). The hypotonic shock reduced the cytosolic pH and increased the external pH in wild type cells but not in cftr -/-. The inhibitory effects DIDS suggest that the acidification of pHi and the alkalinization of pHe induced by hypotonicity in wild type cells could be due to an exit of HCO3-. In conclusion, these results strongly suggested that alkalinization of extracellular medium is a prerequisite condition to trigger the activation of TASK2 during the hypotonic shock. The efflux of HCO3- then alkalinizes the external pH that activated TASK2 channels.
