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.
Sci Rep. 2017 Jan 3;7:39610. doi: 10.1038/srep39610.
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 Ca 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 Ca influx. Extracellular Mg at 2 mM did not significantly affect the shear induced Ca 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.
在研究创伤性脑损伤（TBI）模型中大鼠原代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钙内流。MK-801（N-甲基-D-天冬氨酸受体（NMDAR）通道的特异性孔阻滞剂）抑制了内流，并且在没有激动剂的情况下发生了这种情况。其他 NMDA 开放通道阻滞剂氯胺酮和美金刚也表现出类似的作用。竞争性谷氨酸拮抗剂 AP5 和 GluN2B 选择性抑制剂ifenprodil 降低了 NMDA 激活电流，但对机械诱导的钙内流没有影响。细胞外镁在 2 mM 时对切应力诱导的钙内流没有显著影响，但在 10 mM 时产生了显著的抑制作用。膜片钳实验表明 NMDAR 可被机械激活，且被 MK-801 抑制。NMDAR 的机械敏感性可能在液流的正常生理中发挥作用在神经胶质淋巴系统中，与 TBI 有明显的相关性。
