TASK-1 channels in oligodendrocytes: a role in ischemia mediated disruption.
TASK-1 channels in oligodendrocytes: a role in ischemia mediated disruption.
复制标题
少突胶质细胞中的任务1通道：缺血介导的破坏中的作用。
DOI：
10.1016/j.nbd.2013.03.016
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发表时间：
2013-07
影响因子：
6.1
通讯作者：
Butt A
中科院分区：
文献类型：
--
作者：
Hawkins V;Butt A
少突胶质细胞是中枢神经系统的髓鞘细胞，与神经元一样，对缺血性损伤高度敏感。然而，缺氧/缺血发作期间少突胶质细胞细胞毒性的机制尚不完全清楚。 TASK-1 是介导神经元缺氧去极化的 K+ 渗漏通道。少突胶质细胞中 TASK-1 的表达和功能此前尚未得到解决。在本研究中，我们研究了少突胶质细胞中TASK-1的表达及其在白质缺血性损伤中的作用。使用免疫染色研究了小鼠大脑中少突胶质细胞中 TASK-1 的表达。 TASK-1通道功能通过已建立的药理学和电生理学策略进行鉴定，在视神经（一种典型的白质束）少突胶质细胞的细胞培养物中使用全细胞膜片钳技术。在接受氧糖剥夺（OGD）的分离的完整视神经中检查了 TASK-1 在缺氧中的作用。少突胶质细胞在整个大脑中对 TASK-1 呈强免疫阳性。使用两种公认的抑制 TASK-1 的方法（将细胞外 pH 值降低至 6.4 以及暴露于 TASK-1 选择性抑制剂 anandamide），膜片钳鉴定了少突胶质细胞中的功能性 TASK-1 样漏电流。用甲烷乙醇胺（一种不可水解形式的乙醇胺）孵育视神经，可显着保护少突胶质细胞免受 OGD 中的缺氧破坏和死亡。我们的数据首次证明少突胶质细胞表达功能性 TASK-1 通道，并提供了令人信服的证据，证明少突胶质细胞在缺氧时会导致少突胶质细胞损伤。由于少突胶质细胞损伤是缺血发作的关键因素，因此 TASK-1 可能为中风和白质疾病提供潜在的治疗靶点。 K2P 通道的 TASK-1 亚型参与缺血性神经元损伤。少突胶质细胞是中枢神经系统的髓鞘细胞，对缺血性损伤高度敏感。我们证明了少突胶质细胞中 TASK-1 的功能表达。用 anandamide 抑制 TASK1 可显着防止缺血引起的少突胶质细胞损伤。
Oligodendrocytes are the myelinating cells of the CNS and, like neurons, are highly sensitive to ischemic damage. However, the mechanisms underlying cytotoxicity in oligodendrocytes during hypoxic/ischemic episodes are not fully understood. TASK-1 is a K+ leak channel that mediates hypoxic depolarisation in neurons. The expression and function of TASK-1 in oligodendrocytes had not previously been addressed. In this study, we investigate the expression of TASK-1 in oligodendrocytes and its role in white matter ischemic damage. Expression of TASK-1 in oligodendrocytes was investigated in the mouse brain using immunostaining. TASK-1 channel function was identified by established pharmacological and electrophysiological strategies, using the whole-cell patch clamp technique in cell cultures of oligodendrocytes from the optic nerve, a typical white matter tract. The role of TASK-1 in hypoxia was examined in isolated intact optic nerves subjected to oxygen glucose deprivation (OGD). Oligodendrocytes are strongly immunopositive for TASK-1 throughout the brain. Patch-clamp identified functional TASK-1-like leak currents in oligodendrocytes using two recognised means of inhibiting TASK-1, decreasing extracellular pH to 6.4 and exposure to the TASK-1 selective inhibitor anandamide. Incubation of optic nerves with methanandamide, a non-hydrolysable form of anandamide, significantly protected oligodendrocytes against hypoxic disruption and death in OGD. Our data demonstrate for the first time that oligodendrocytes express functional TASK-1 channels and provide compelling evidence they contribute to oligodendrocyte damage in hypoxia. Since oligodendrocyte damage is a key factor in ischemic episodes, TASK-1 may provide a potential therapeutic target in stroke and white matter disease. TASK-1 subtype of K2P channel is involved in ischemic neuronal damage. Oligodendrocytes, the myelinating cells of the CNS, are highly sensitive to ischemic damage. We demonstrate functional expression of TASK-1 in oligodendrocytes. Inhibition of TASK1 with anandamide significantly protected against oligodendrocyte damage in response to ischemia.
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影响因子：
5.5
作者：
Kang, DW;Han, JH;Kim, DH
通讯作者：
Kim, DH
影响因子：
6.2
作者：
Feldman, Daniel H.;Horiuchi, Makoto;Keachie, Krista;Mccauley, Erica;Bannerman, Peter;Itoh, Aki;Itoh, Takayum;Pleasure, David
通讯作者：
Pleasure, David
影响因子：
4.8
作者：
Czirják, G;Enyedi, P
通讯作者：
Enyedi, P
影响因子：
6.2
作者：
BUTT, AM;IBRAHIM, M;BERRY, M
通讯作者：
BERRY, M
DOI：
10.1111/j.1582-4934.2006.tb00289.x
发表时间：
2006-01
影响因子：
5.3
作者：
Butt AM;Kalsi A
通讯作者：
Kalsi A