Ischemic postconditioning (PostC) is known to reduce cerebral ischemia/reperfusion (I/R) injury; however, whether the opening of mitochondrial ATP-dependent potassium (mito-K_ATP) channels and mitochondrial permeability transition pore (mPTP) cause the depolarization of the mitochondrial membrane that remains unknown. We examined the involvement of the mito-K_ATP channel and the mPTP in the PostC mechanism. Ischemic PostC consisted of three cycles of 15 s reperfusion and 15 s re-ischemia, and was started 30 s after the 7.5 min ischemic load. We recorded N-methyl-d-aspartate receptors (NMDAR)-mediated currents and measured cytosolic Ca²⁺ concentrations, and mitochondrial membrane potentials in mouse hippocampal pyramidal neurons. Both ischemic PostC and the application of a mito-K_ATP channel opener, diazoxide, reduced NMDAR-mediated currents, and suppressed cytosolic Ca²⁺ elevations during the early reperfusion period. An mPTP blocker, cyclosporine A, abolished the reducing effect of PostC on NMDAR currents. Furthermore, both ischemic PostC and the application of diazoxide potentiated the depolarization of the mitochondrial membrane potential. These results indicate that ischemic PostC suppresses Ca²⁺ influx into the cytoplasm by reducing NMDAR-mediated currents through mPTP opening. The present study suggests that depolarization of the mitochondrial membrane potential by opening of the mito-K_ATP channel is essential to the mechanism of PostC in neuroprotection against anoxic injury.

已知缺血后处理 (PostC) 可减少脑缺血/再灌注 (I/R) 损伤；然而，线粒体 ATP 依赖性钾 (mito-K _ATP ) 通道和线粒体通透性转换孔 (mPTP) 的开放是否会导致线粒体膜的去极化尚不清楚。我们检查了mito-K _ATP通道和mPTP 在PostC 机制中的参与。缺血 PostC 由 15 秒再灌注和 15 秒再缺血三个周期组成，并在 7.5 分钟缺血负荷后 30 秒开始。我们记录了N-甲基-d-天冬氨酸受体 (NMDAR) 介导的电流并测量了细胞溶质 Ca ²⁺小鼠海马锥体神经元的浓度和线粒体膜电位。缺血性 PostC 和 mito-K _ATP通道开放剂二氮嗪的应用均降低了 NMDAR 介导的电流，并在早期再灌注期间抑制了细胞溶质 Ca ^{2+的升高。}mPTP 阻滞剂环孢素 A 消除了 PostC 对 NMDAR 电流的降低作用。此外，缺血性 PostC 和二氮嗪的应用都增强了线粒体膜电位的去极化。这些结果表明缺血性 PostC 抑制 Ca ²⁺通过减少通过 mPTP 开口的 NMDAR 介导的电流流入细胞质。本研究表明，通过打开 mito-K _ATP通道使线粒体膜电位去极化对于 PostC 对缺氧损伤的神经保护机制至关重要。