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Biochem Biophys Res Commun. 2013 Mar 22;432(4):701-6. doi: 10.1016/j.bbrc.2013.01.090. Epub 2013 Jan 31.

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

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Department of Otorhinolaryngology, QiLu Hospital, Shandong University, Jinan, China.


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.

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