Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Mol Neurosci. 2012 Feb;46(2):384-92. doi: 10.1007/s12031-011-9598-z. Epub 2011 Jul 26.
Astrocytes play an active and important role in the pathophysiology of cerebral ischemia. We have previously shown that mature hipppocampal astrocytes functionally express two-pore domain K(+) channel TREK-1, which significantly contributes to the passive conductance and help to set the negative resting membrane potential essential for the optimal operation of some astrocytic homeostatic functions. However, its expression under ischemic conditions remains to be determined. In this study, we examined the expression of TREK-1 in rat brain under physiological and focal ischemia conditions. The results show that TREK-1 was broadly expressed on astrocytes and neurons in the cortex, CA1 region of hippocampus. After middle cerebral artery occlusion induced focal ischemia, the TREK-1 expression was significantly increased at days 3, 7 and 30 following reperfusion, which correlated with reactive astrogliosis in the cortex and hippocampus. Cultured cortical astrocytes also express TREK-1. TREK-1 inhibitor quinine inhibited the proliferation of astrocytes exposed to hypoxia condition. These data provide evidence showing the astrocytic TREK-1 involvement in ischemia pathology.
星形胶质细胞在脑缺血的病理生理学中发挥着积极而重要的作用。我们之前已经表明，成熟的海马星形胶质细胞在功能上表达双孔域钾(K+)通道 TREK-1，这对被动电导有重要贡献，并有助于建立负的静息膜电位，这对一些星形胶质细胞稳态功能的最佳运作至关重要。然而，其在缺血条件下的表达仍有待确定。在这项研究中，我们检查了在生理和局灶性缺血条件下大鼠脑内 TREK-1 的表达。结果表明，TREK-1 在皮质和海马 CA1 区的星形胶质细胞和神经元上广泛表达。大脑中动脉闭塞诱导局灶性缺血后，再灌注后第 3、7 和 30 天，TREK-1 的表达明显增加，与皮质和海马的反应性星形胶质增生相关。培养的皮质星形胶质细胞也表达 TREK-1。TREK-1 抑制剂奎宁抑制了暴露于低氧条件下的星形胶质细胞的增殖。这些数据提供了证据表明星形胶质细胞 TREK-1 参与了缺血性病理。
