These authors contributed equally to this work.
TRPC6 inhibited NMDA receptor activities and protected neurons from ischemic excitotoxicity
Article first published online: 1 NOV 2012
© 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 6, pages 1010–1018, December 2012
How to Cite
J. Neurochem. (2012) 123, 1010–1018.
- Issue published online: 4 DEC 2012
- Article first published online: 1 NOV 2012
- Accepted manuscript online: 8 OCT 2012 12:10PM EST
- Manuscript Accepted: 27 SEP 2012
- Manuscript Revised: 26 SEP 2012
- Manuscript Received: 27 JUN 2012
- focal ischemia;
- transgenic mice;
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.