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Modulation of K2P3.1 (TASK‐1) and K2P9.1 (TASK‐3) by reactive oxygen species
Author(s) -
Kim Donghee,
Papreck Justin R.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb574
Subject(s) - reactive oxygen species , chemistry , xanthine oxidase , microbiology and biotechnology , superoxide , extracellular , intracellular , biophysics , biochemistry , biology , enzyme
Reactive oxygen species (ROS) may mediate hypoxia‐induced vasoconstriction of the pulmonary arteries and excitation of O2‐sensitive cells. In these cells, TASKs contribute to the background K+ current that is inhibited by hypoxia. To determine the role of ROS in hypoxic inhibition of TASK, we studied the effects of hydrogen peroxide (H2O2) and superoxide radical on TASKs expressed in HeLa cells. H2O2 applied to inside‐out, but outside‐out, patches activated TASK‐1, TASK‐3 and TASK‐1/3 heteromer starting at ~16 mM. H2O2 did not affect other K2P channels (TREK‐2, TASK‐2, TALK‐2, TRESK). Dithiothreitol and MTSEA had no effect on basal TASK activity, and did not block the H2O2‐induced increase in channel activity. H2O2 increased the activity of TASK mutant in which the C‐terminus of TASK‐3 was replaced with that of TREK‐2. Xanthine/xanthine oxidase mixture used to generate superoxide radical showed no effect on TASKs from either side of the membrane, but activated TASK‐2 from the extracellular side. In rat cerebellar granule neurons, adrenal chromaffin cells and carotid body glomus cells that express TASK‐like channels, intracellular H2O2 (>16 mM) activated the channels, similar to that observed with cloned TASKs. Although H2O2 is able to activate TASKs, the high [H2O2] required for this effect suggests that H2O2 is unlikely to act as a signal mediator for hypoxia.