PMID- 28400714
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 11
DP  - 2017
TI  - Deletion of TRPC6 Attenuates NMDA Receptor-Mediated Ca(2+) Entry and 
      Ca(2+)-Induced Neurotoxicity Following Cerebral Ischemia and Oxygen-Glucose 
      Deprivation.
PG  - 138
LID - 10.3389/fnins.2017.00138 [doi]
LID - 138
AB  - Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na(+) 
      and Ca(2+) and are widely expressed in the brain. In this study, the role of 
      TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose 
      deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) 
      mice cortical neurons following I/R and in primary neurons with OGD, and that 
      deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- 
      /neurotoxin-induced neuronal death. Using live-cell imaging to examine 
      intracellular Ca(2+) levels ([Ca(2+)] (i) ), we found that OGD induced a 
      significant higher increase in glutamate-evoked Ca(2+) influx compared to 
      untreated control and such an increase was reduced by TRPC6 deletion. Enhancement 
      of TRPC6 expression using AdCMV-TRPC6-GFP infection in WT neurons increased 
      [Ca(2+)] (i) in response to glutamate application compared to AdCMV-GFP control. 
      Inhibition of N-methyl-d-aspartic acid receptor (NMDAR) with MK801 decreased 
      TRPC6-dependent increase of [Ca(2+)] (i) in TRPC6 infected cells, indicating that 
      such a Ca(2+) influx was NMDAR dependent. Furthermore, TRPC6-dependent Ca(2+) 
      influx was blunted by blockade of Na(+) entry in TRPC6 infected cells. Finally, 
      OGD-enhanced Ca(2+) influx was reduced, but not completely blocked, in the 
      presence of voltage-dependent Na(+) channel blocker tetrodotoxin (TTX) and 
      dl-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) blocker CNQX. 
      Altogether, we concluded that I/R-induced brain damage was, in part, due to 
      upregulation of TRPC6 in cortical neurons. We postulate that overexpression of 
      TRPC6 following I/R may induce neuronal death partially through TRPC6-dependent 
      Na(+) entry which activated NMDAR, thus leading to a damaging Ca(2+) overload. 
      These findings may provide a potential target for future intervention in 
      stroke-induced brain damage.
FAU - Chen, Jin
AU  - Chen J
AD  - Division of Neuroscience, Burnett School of Biomedical Sciences, College of 
      Medicine, University of Central Florida Orlando, FL, USA.
FAU - Li, Zhaozhong
AU  - Li Z
AD  - Division of Neuroscience, Burnett School of Biomedical Sciences, College of 
      Medicine, University of Central Florida Orlando, FL, USA.
FAU - Hatcher, Jeffery T
AU  - Hatcher JT
AD  - Division of Neuroscience, Burnett School of Biomedical Sciences, College of 
      Medicine, University of Central Florida Orlando, FL, USA.
FAU - Chen, Qing-Hui
AU  - Chen QH
AD  - Department of Kinesiology and Integrative Physiology, Michigan Technological 
      University Houghton, MI, USA.
FAU - Chen, Li
AU  - Chen L
AD  - Department of Clinical Laboratory, The First Central Hospital of Tianjin Tianjin, 
      China.
FAU - Wurster, Robert D
AU  - Wurster RD
AD  - Department of Cellular and Molecular Physiology, Stritch School of Medicine, 
      Loyola University Maywood, IL, USA.
FAU - Chan, Sic L
AU  - Chan SL
AD  - Division of Neuroscience, Burnett School of Biomedical Sciences, College of 
      Medicine, University of Central Florida Orlando, FL, USA.
FAU - Cheng, Zixi
AU  - Cheng Z
AD  - Division of Neuroscience, Burnett School of Biomedical Sciences, College of 
      Medicine, University of Central FloridaOrlando, FL, USA; Division of Metabolic 
      and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of 
      Medicine, University of Central FloridaOrlando, FL, USA.
LA  - eng
PT  - Journal Article
DEP - 20170328
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC5368256
OTO - NOTNLM
OT  - Ca2+
OT  - NMDA
OT  - TRPC6
OT  - ischemia
OT  - neurotoxicity
OT  - oxygen-glucose deprivation (OGD)
EDAT- 2017/04/13 06:00
MHDA- 2017/04/13 06:01
PMCR- 2017/01/01
CRDT- 2017/04/13 06:00
PHST- 2017/01/21 00:00 [received]
PHST- 2017/03/06 00:00 [accepted]
PHST- 2017/04/13 06:00 [entrez]
PHST- 2017/04/13 06:00 [pubmed]
PHST- 2017/04/13 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2017.00138 [doi]
PST - epublish
SO  - Front Neurosci. 2017 Mar 28;11:138. doi: 10.3389/fnins.2017.00138. eCollection 
      2017.