TRPC6 inhibited NMDA receptor activities and protected neurons from ischemic excitotoxicity

Authors

  • Hongyu Li,

    1. Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, State Key Laboratory of Neuroscience, Shanghai, China
    2. The Graduate School, Chinese Academy of Science, Shanghai, China
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Junbo Huang,

    1. Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, State Key Laboratory of Neuroscience, Shanghai, China
    2. The Graduate School, Chinese Academy of Science, Shanghai, China
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Wanlu Du,

    1. Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, State Key Laboratory of Neuroscience, Shanghai, China
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Caixia Jia,

    1. Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, State Key Laboratory of Neuroscience, Shanghai, China
    Search for more papers by this author
  • Hailan Yao,

    1. Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, State Key Laboratory of Neuroscience, Shanghai, China
    Search for more papers by this author
  • Yizheng Wang

    Corresponding author
    • Laboratory of Neural Signal Transduction, Institute of Neuroscience, SIBS, State Key Laboratory of Neuroscience, Shanghai, China
    Search for more papers by this author

Address correspondence and reprint requests to Yizheng Wang, Laboratory of neural signal transduction, Institute of Neuroscience, SIBS, Chinese Academy of Science. 320 Yue-Yang Road, Shanghai, 200031 China. E-mail: yzwang@ion.ac.cn

Abstract

Excitotoxicity induced by NMDA receptor-mediated intracellular Ca2+ ([Ca2+]i) overload is a major cause of delayed neuronal death in cerebral ischemia. Transient receptor potential canonical (TRPC) 6 protects neurons from ischemic brain damage. However, the mechanisms by which TRPC6 protects neurons are largely unknown. Here, we reported that TRPC6 suppressed the [Ca2+]i elevation induced by NMDA and protected neurons from excitotoxicity. Over-expressing or down-regulating TRPC6 suppressed or aggravated Ca2+ overload under excitotoxicity, respectively. TRPC6 protected cultured neurons from damage caused by NMDA toxicity or oxygen glucose deprivation (OGD). Moreover, the infarct volume in TRPC6 transgenic (Tg) mice was smaller than that in wild-type (WT) littermates. The TRPC6 Tg mice had better behavior performance and lower mortality than their WT littermates. Thus, TRPC6 inhibited NMDA receptor-triggered neurotoxicity and protected neurons from ischemic brain damage. Increase in TRPC6 activity could be a potential strategy for stroke prevention and therapy.

Ancillary