Extracellular acidic pH-activated, outward rectifying chloride currents can be regulated by reactive oxygen species in human THP-1 monocytes

Extracellular acidic pH-activated chloride channels (ICl,acid) have been found in a variety of mammalian cells. In the present study, the expression and regulation of ICl,acid were investigated in THP-1 cells. Patch clamp recordings demonstrated that an extracellular acidic solution induced an outward rectified current, which could be blocked by the Cl− channel blocker. The currents exhibited time-dependent facilitation and inactivation. The relative anion permeability of this current followed the sequence Cl− > Br− > I− > gluconate. NADPH oxidase inhibitors did not decrease pH 4.4-induced currents. However, reactive oxygen species (ROS) scavengers and mitochondrial inhibitors inhibited pH 4.4-induced currents. Fluorescence imaging of intracellular ROS and mitochondrial activity confirmed these findings. We conclude that ICl,acid occurs in human THP-1 cells and that ICl,acid may be regulated by intracellular ROS mainly originating from mitochondria.

► An acidic pH-activated outward chloride channel (ICl,acid) was found in THP-1 cells. ► NADPH oxidase inhibitors did not decrease pH 4.4-induced currents. ► ROS scavengers and mitochondrial inhibitors inhibited pH 4.4-induced currents. ► ICl,acid could be regulated by intracellular ROS originating from mitochondria.