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Sci Rep. 2017 Jan 3;7:39610. doi: 10.1038/srep39610.

Mechanical stress activates NMDA receptors in the absence of agonists.

Author information

1
Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York, 14260, USA.
2
Department of Mechanical and Aerospace Engineering, University at Buffalo, Buffalo, New York 14260, USA.
3
Department of Biochemistry, University at Buffalo, Buffalo, New York 14260, USA.

Abstract

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.

PMID:
28045032
PMCID:
PMC5206744
DOI:
10.1038/srep39610
[Indexed for MEDLINE]
Free PMC Article

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