Abstract
It has recently been reported that extracellular acid pH activates anion channels in several cell types. In the present study, we also found functional expression of proton-activated Cl − channel in human epithelial HeLa cells. Whole-cell currents were rapidly activated by extracellular acidic solution (pH < 5.0) in a reversible manner. This current exhibited prominent outwardly rectification under symmetrical Cl − conditions, time-dependent activation at positive potentials, and low-field anion permeability sequence of I − > Br − > Cl − > aspartate −. A Cl − channel blocker, 4, 4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) or phloretin, could inhibit the current in a concentration-dependent manner with the IC50 value of 0.12 or 18.6 μM, respectively. Anion selectivity and sensitivity to Cl − channel blockers of this proton-activated current are similar to those of the volume-sensitive outwardly rectifying (VSOR) Cl − channel current in HeLa cells. However, the other properties are distinct from those of the VSOR Cl − channel which is inhibited by acid and exhibits modest outward rectification and inactivation kinetics at positive potentials. [J Physiol Sci. 2006;56 Suppl:S116]
