title: Mechanical stress activates NMDA receptors in the absence of agonists.
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.
authors.affiliation: 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.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Maneshi
authors.affiliation: Department of Biochemistry, University at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Maki
authors.affiliation: Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York, 14260, USA.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Gnanasambandam
authors.affiliation: Department of Biochemistry, University at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Belin
authors.affiliation: Department of Biochemistry, University at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Popescu
authors.affiliation: Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York, 14260, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Sachs
authors.affiliation: 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.
authors.forename: Susan Z
authors.initials: SZ
authors.lastname: Hua
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells; D020013:Calcium Signaling; D003412:Cricetulus; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D010812:Physical Stimulation; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate