Search

Background K2P channels are tightly regulated by different stimuli including variations of external and internal pH. pH sensitivity relies on proton-sensing residues that influence channel gating and activity. Gene inactivation in the mouse is a revealing implication of K2P channels in many physiological functions ranging from hormone secretion to central respiratory adaptation. Surprisingly, only a few phenotypic traits of these mice have yet been directly related to the pH sensitivity of K2P channels.

We have previously shown that K+-selective TASK2 channels and swelling-activated Cl−currents are involved in a regulatory volume decrease (RVD; Barriere H, Belfodil R, Rubera I, Tauc M, Lesage F, Poujeol C, Guy N, Barhanin J, Poujeol P. J Gen Physiol 122: 177–190, 2003; Belfodil R, Barriere H, Rubera I, Tauc M, Poujeol C, Bidet M, Poujeol P. Am J Physiol Renal Physiol 284: F812–F828, 2003). The aim of this study was to determine the mechanism responsible for the activation of TASK2 channels during RVD in proximal cell lines from mouse kidney. For this purpose, the patch-clamp whole-cell technique was used to test the effect of pH and the buffering capacity of external bath on Cl−and K+currents during hypotonic shock. In the presence of a high buffer concentration (30 mM HEPES), the cells did not undergo RVD and did not develop outward K+currents (TASK2). Interestingly, the hypotonic shock reduced the cytosolic pH (pHi) and increased the external pH (pHe) in wild-type but not in cftr−/−cells. The inhibitory effect of DIDS suggests that the acidification of pHiand the alkalinization of pHeinduced by hypotonicity in wild-type cells could be due to an exit of HCO3−. In conclusion, these results indicate that Cl−influx will be the driving force for HCO3−exit through the activation of the Cl−/HCO3−exchanger. This efflux of HCO3−then alkalinizes pHe, which in turn activates TASK2 channels.