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Ca 2+ modulation of volume‐regulated anion channels: evidence for colocalization with store‐operated channels
Author(s) -
Lemonnier Loïc,
Prevarskaya Natalia,
Shuba Yaroslav,
Vanden Abeele Fabien,
Nilius Bernd,
Mazurier Joël,
Skryma Roman
Publication year - 2002
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/fj.01-0383fje
Subject(s) - extracellular , thapsigargin , colocalization , biophysics , chemistry , ruthenium red , intracellular , endoplasmic reticulum , patch clamp , membrane , microbiology and biotechnology , biochemistry , calcium , biology , receptor , organic chemistry
Ca 2+ regulation of Cl − current induced by cell swelling (I Cl , swell ) in response to hypotonicity was studied in human prostate cancer epithelial cells (LNCaP) by using the patch‐clamp technique. Increase of global intracellular Ca 2+ ([Ca 2+ ] in ) to 1 μM as well as variations of the extracellular Ca 2+ ([Ca 2+ ] out ) in the 0 to 10 mM range did not affect time course of the development, maximal amplitude, rectification properties, and kinetics of I Cl,swell . However, the presence of 0.1 μM thapsigargin (TG), an inhibitor of endoplasmic reticulum (ER) Ca 2+ pump, resulted in a more than 50% inhibition of I Cl,swell . The blockade of plasma membrane store‐operated channels (SOCs), activated in the presence of TG, by 2 mM Ni 2+ prevented TG‐conferred I Cl,swell inhibition by extracellular Ca 2+ . In the presence of TG and Ca 2+ , the cells failed to exhibit regulatory volume decrease. We conclude that interaction between volume‐regulated anion channels (VRACs) carrying I Cl,swell and Ca 2+ occurs in the microdomains from the inner surface of the membrane that are not accessible to the changes in [Ca 2+ ]in, but can be readily reached by Ca 2+ entering the cell via plasma membrane, especially through SOCs. Preferred access of SOC‐transported Ca 2+ to VRAC suggests colocalization of these channels in the cell membrane.

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