Send to

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

Mechanical stress activates NMDA receptors in the absence of agonists.

Author information

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


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center