Cortical pyramidal neurons show rapid and irreversible membrane depolarization in response to oxygen-glucose depolarization (OGD). In this study, we investigated cellular mechanisms responsible for rapid depolarization caused by OGD in layer III pyramidal neurons of the mouse somatosensory cortex. When OGD solution was perfused in the presence of Ca2+ chelator and inhibitors of ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) in the pipette solution or in the presence of inhibitors of NMDA receptors (NMDARs), voltage-gated Ca2+ channels (VGCCs), and canonical transient receptor potential (TRPC) channels in the perfusion solution, the latency of the rapid depolarization was significantly prolonged compared to the control. In addition, when OGD solution was perfused in the presence of scavengers of nitric oxide and reactive oxygen species in the perfusion solution or in the presence of calcineurin inhibitors in the pipette solution, the latency of the rapid depolarization was significantly prolonged compared to the control. These data indicate that OGD-induced intracellular Ca2+ increases mediated by Ca2+ influx through NMDARs, VGCCs and TRPC channels as well as by Ca2+ release from RyRs and IP3Rs lead to mitochondrial impairment, which may facilitate the generation of the rapid depolarization via dysfunction of Na+-K+-ATPase due to decreased ATP production.

中文翻译：

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躯体感觉皮层 III 层锥体细胞缺氧和缺糖引起快速去极化的细胞机制

皮质锥体神经元响应氧-葡萄糖去极化 (OGD) 显示出快速且不可逆的膜去极化。在这项研究中，我们研究了小鼠体感皮层 III 层锥体神经元中由 OGD 引起的快速去极化的细胞机制。当 OGD 溶液在移液管溶液中存在 Ca2+ 螯合剂和兰尼碱受体 (RyRs) 抑制剂和肌醇 1,4,5-三磷酸受体 (IP3Rs) 或存在 NMDA 受体抑制剂 (NMDARs) 的情况下灌注时，电压门控 Ca2+ 通道 (VGCC) 和灌注溶液中的经典瞬时受体电位 (TRPC) 通道，与对照相比，快速去极化的潜伏期显着延长。此外，当 OGD 溶液在灌注溶液中存在一氧化氮和活性氧清除剂或移液管溶液中存在钙调磷酸酶抑制剂的情况下灌注时，与对照相比，快速去极化的潜伏期显着延长。这些数据表明，OGD 诱导的细胞内 Ca2+ 增加由 Ca2+ 通过 NMDARs、VGCC 和 TRPC 通道的流入以及 RyRs 和 IP3Rs 的 Ca2+ 释放介导导致线粒体损伤，这可能促进通过 Na+- 功能障碍产生的快速去极化由于 ATP 产生减少，K+-ATPase。