Mechanical stress activates NMDA receptors in the absence of agonists.
Mechanical stress activates NMDA receptors in the absence of agonists.
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DOI：
10.1038/srep39610
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发表时间：
2017-01-03
影响因子：
4.6
通讯作者：
Hua SZ
中科院分区：
文献类型：
--
作者：
Maneshi MM;Maki B;Gnanasambandam R;Belin S;Popescu GK;Sachs F;Hua SZ
在研究创伤性脑损伤（TBI）模型中原代大鼠星形胶质细胞对流体切应力的生理反应时，我们发现切应力诱导了Ca 2+内流。内流被MK-801抑制，MK-801是一种N-甲基-D-天冬氨酸受体（NMDAR）通道的特异性孔阻断剂，并且这在不存在激动剂的情况下发生。其他NMDA开放通道阻断剂氯胺酮和美金刚胺显示出类似的效果。竞争性谷氨酸拮抗剂AP 5和GluN 2B选择性抑制剂ifenprodil降低NMDA激活电流，但对机械诱导的Ca 2+内流没有影响。细胞外Mg 2+在2 mM没有显着影响剪切诱导的Ca 2+内流，但在10 mM，它产生了显着的抑制。膜片钳实验显示NMDAR的机械激活和MK-801的抑制。NMDARs的机械敏感性可能在胶质淋巴系统流体流动的正常生理中起作用，并且与TBI具有明显的相关性。
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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影响因子：
3.7
作者：
Drew, Liam J.;Rugiero, Francois;Cesare, Paolo;Gale, Jonathan E.;Abrahamsen, Bjarke;Bowden, Sarah;Heinzmann, Sebastian;Robinson, Michelle;Brust, Andreas;Colless, Barbara;Lewis, Richard J.;Wood, John N.
通讯作者：
Wood, John N.
影响因子：
3.6
作者：
Emnett, Christine M.;Eisenman, Lawrence N.;Mennerick, Steven
通讯作者：
Mennerick, Steven
影响因子：
4.4
作者：
Jessen NA;Munk AS;Lundgaard I;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
64.8
作者：
Coste, Bertrand;Xiao, Bailong;Santos, Jose S.;Syeda, Ruhma;Grandl, Joerg;Spencer, Kathryn S.;Kim, Sung Eun;Schmidt, Manuela;Mathur, Jayanti;Dubin, Adrienne E.;Montal, Mauricio;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
影响因子：
4.6
作者：
BRODE, HL
通讯作者：
BRODE, HL