Novel mechanistic insights and potential therapeutic impact of trpc6 in neurovascular coupling and ischemic stroke

Shashank Shekhar, Yedan Liu, Shaoxun Wang, Huawei Zhang, Xing Fang, Jin Zhang, Letao Fan, Baoying Zheng, Richard J. Roman, Zhen Wang, Fan Fan, George W. Booz

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates the cAMP (adenosine 3’,5’‐cyclic monophosphate) response element‐binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of N‐methyl‐D‐aspartate (NMDA) receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells, such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood–brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence‐based cell‐specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

Original languageEnglish (US)
Article number2074
Pages (from-to)1-15
Number of pages15
JournalInternational journal of molecular sciences
Issue number4
StatePublished - Feb 2 2021
Externally publishedYes


  • Blood–brain barrier
  • CAMP response element‐binding protein
  • Calcium signaling
  • Ischemic stroke
  • Neuroprotection
  • Transient receptor potential cation channels

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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