LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death

Mol Cell. 2002 Jan;9(1):163-73. doi: 10.1016/s1097-2765(01)00438-5.


Redox status changes exert critical impacts on necrotic/apoptotic and normal cellular processes. We report here a widely expressed Ca2+-permeable cation channel, LTRPC2, activated by micromolar levels of H2O2 and agents that produce reactive oxygen/nitrogen species. This sensitivity of LTRPC2 to redox state modifiers was attributable to an agonistic binding of nicotinamide adenine dinucleotide (beta-NAD+) to the MutT motif. Arachidonic acid and Ca2+ were important positive regulators for LTRPC2. Heterologous LTRPC2 expression conferred susceptibility to death on HEK cells. Antisense oligonucleotide experiments revealed physiological involvement of "native" LTRPC2 in H2O2- and TNFalpha-induced Ca2+ influx and cell death. Thus, LTRPC2 represents an important intrinsic mechanism that mediates Ca2+ and Na+ overload in response to disturbance of redox state in cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Line
  • Humans
  • Ion Channels*
  • Membrane Proteins*
  • Mice
  • Nitric Oxide Donors / pharmacology
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • TRPM Cation Channels
  • Tumor Necrosis Factor-alpha / metabolism


  • Calcium Channels
  • Ion Channels
  • Membrane Proteins
  • Nitric Oxide Donors
  • Reactive Oxygen Species
  • TRPM Cation Channels
  • TRPM2 protein, human
  • Tumor Necrosis Factor-alpha
  • Calcium