title: Extracellular acidic pH-activated, outward rectifying chloride currents can be regulated by reactive oxygen species in human THP-1 monocytes.
abstract: 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.
authors: Department of Otorhinolaryngology, QiLu Hospital, Shandong University, Jinan, China.
authors: Zhi-jie
authors: ZJ
authors: Fu
authors: Xue-zhong
authors: XZ
authors: Li
authors: Qi-rong
authors: QR
authors: Wang
authors: Li
authors: L
authors: Shi
authors: Li-qiang
authors: LQ
authors: Zhang
authors: Xin-liang
authors: XL
authors: Pan
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000143:Acids / Q000737:chemistry; D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012996:Solutions
chemical_list: D000143:Acids; D018118:Chloride Channels; D017382:Reactive Oxygen Species; D012996:Solutions; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid