Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose

• Published in: The Journal of biological chemistry Vol. 277; no. 26; p. 23150
• Main Authors: Wehage, Edith, Eisfeld, Jörg, Heiner, Inka, Jüngling, Eberhard, Zitt, Christof, Lückhoff, Andreas
• Format: Journal Article
• Language: English
• Published: United States 28.06.2002
• Subjects: Adenosine Diphosphate Ribose - physiology; Adult; Base Sequence; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - genetics; Calcium Channels - metabolism; Cloning, Molecular; Humans; Hydrogen Peroxide - pharmacology; Ion Channels; Membrane Proteins; Molecular Sequence Data; NAD - pharmacology; Oxidative Stress; TRPM Cation Channels
• ISSN: 0021-9258
• DOI: 10.1074/jbc.M112096200

LTRPC2 is a cation channel recently reported to be activated by adenosine diphosphate-ribose (ADP-ribose) and NAD. Since ADP-ribose can be formed from NAD and NAD is elevated during oxidative stress, we studied whole cell currents and increases in the intercellular free calcium concentration ([Ca(2+)](i)) in long transient receptor potential channel 2 (LTRPC2)-transfected HEK 293 cells after stimulation with hydrogen peroxide (H(2)O(2)). Cation currents carried by monovalent cations and Ca(2+) were induced by H(2)O(2) (5 mm in the bath solution) as well as by intracellular ADP-ribose (0.3 mm in the pipette solution) but not by NAD (1 mm). H(2)O(2)-induced currents developed slowly after a characteristic delay of 3-6 min and receded after wash-out of H(2)O(2). [Ca(2+)](i) was rapidly increased by H(2)O(2) in LTRPC2-transfected cells as well as in control cells; however, in LTRPC2-transfected cells, H(2)O(2) evoked a second delayed rise in [Ca(2+)](i). A splice variant of LTRPC2 with a deletion in the C terminus (amino acids 1292-1325) was identified in neutrophil granulocytes. This variant was stimulated by H(2)O(2) as the wild type. However, it did not respond to ADP-ribose. We conclude that activation of LTRPC2 by H(2)O(2) is independent of ADP-ribose and that LTRPC2 may mediate the influx of Na(+) and Ca(2+) during oxidative stress, such as the respiratory burst in granulocytes.