Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Mol Neurosci. 2013 Mar;49(3):499-506. doi: 10.1007/s12031-012-9875-5. Epub 2012 Aug 16.
Astrocytes play a fundamental role in the pathogenesis of ischemic neuronal death. The optimal operation of electrogenic astrocytic transporters and exchangers for some well-defined astrocyte brain homeostatic functions depends on the presence of K(+) channels in the cell membranes and the hyperpolarized membrane potential. Our previous study showed that astrocytes functionally express two-pore domain K(+) channel TREK-1, which helps to set the negative resting membrane potential. However, the roles of TREK-1 on astrocytic function under normal and ischemic conditions remain unclear. In this study, we investigated the expression of TREK-1 protein on cultured astrocytes and the effect of TREK-1 activity on astrocytic glutamate clearance capacity and release of s100β after simulated ischemic insult. TREK-1 immunoreactivity was up-regulated after hypoxia. Suppression of TREK-1 activity inhibited the glutamate clearance capability, enhanced the inflammatory secretion of astrocytes derived s100β and led to increased neuronal apoptosis after ischemic insult. Our results suggest that TREK-1 activity is involved in astrocytic function and neuronal survival. This would provide evidence showing astrocytic TREK-1 involvement in ischemia pathology which may serve as a potential therapeutic target in stroke.
星形胶质细胞在缺血性神经元死亡的发病机制中起着至关重要的作用。一些明确的星形胶质细胞脑内稳态功能的电活性星形胶质细胞转运体和交换体的最佳运作依赖于细胞膜中 K(+)通道的存在和超极化的膜电位。我们之前的研究表明，星形胶质细胞功能性表达双孔域 K(+)通道 TREK-1，有助于设定负的静息膜电位。然而，TREK-1 在正常和缺血条件下对星形胶质细胞功能的作用尚不清楚。在这项研究中，我们研究了培养的星形胶质细胞中 TREK-1 蛋白的表达以及 TREK-1 活性对星形胶质细胞谷氨酸清除能力和模拟缺血性损伤后 s100β 释放的影响。缺氧后 TREK-1 免疫反应性上调。抑制 TREK-1 活性抑制了谷氨酸的清除能力，增强了星形胶质细胞衍生的 s100β 的炎症分泌，并导致缺血性损伤后神经元凋亡增加。我们的结果表明，TREK-1 活性参与星形胶质细胞功能和神经元存活。这将为星形胶质细胞 TREK-1 参与缺血性病理提供证据，这可能成为中风的潜在治疗靶点。
