Mechanical stress activates NMDA receptors in the absence of agonists

Article English OPEN
Maneshi, Mohammad Mehdi ; Maki, Bruce ; Gnanasambandam, Radhakrishnan ; Belin, Sophie ; Popescu, Gabriela K. ; Sachs, Frederick ; Hua, Susan Z. (2017)
  • Publisher: Nature Publishing Group
  • Journal: Scientific Reports, volume 7 (issn: 2045-2322, eissn: 2045-2322)
  • Related identifiers: pmc: PMC5206744, doi: 10.1038/srep39610
  • Subject: Article
    mesheuropmc: nervous system

While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca2+ influx. Extracellular Mg2+ at 2 mM did not significantly affect the shear induced Ca2+ influx, but at 10 mM it produced significant inhibition. Patch clamp experiments showed mechanical activation of NMDAR and inhibition by MK-801. The mechanical sensitivity of NMDARs may play a role in the normal physiology of fluid flow in the glymphatic system and it has obvious relevance to TBI.
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