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.
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.
Wehage
Edith
E
Institute of Physiology, Medical Faculty, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany.
Eisfeld
Jörg
J
Heiner
Inka
I
Jüngling
Eberhard
E
Zitt
Christof
C
Lückhoff
Andreas
A
D000246:Adenosine Diphosphate Ribose / Q000502:physiology*; D000328:Adult; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007473:Ion Channels; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009243:NAD / Q000494:pharmacology; D018384:Oxidative Stress; D050053:TRPM Cation Channels
D015220:Calcium Channels; D007473:Ion Channels; D008565:Membrane Proteins; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D006861:Hydrogen Peroxide; D002118:Calcium