KCa2 channels activation prevents [Ca2+]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia.
KCa2 channels activation prevents [Ca2+]i deregulation and reduces neuronal death following glutamate toxicity and cerebral ischemia.
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KCA2通道激活可防止[Ca2+] I失调并减少谷氨酸毒性和脑缺血后神经元死亡。
DOI：
10.1038/cddis.2011.30
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发表时间：
2011-04-21
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
谷氨酸受体偶联钙通道的激活加剧和随后的细胞内钙（[Ca2+]i）增加是急性和慢性神经系统疾病中神经元细胞死亡的标志。在这里，我们表明，病理[Ca2+]i失调发生后，谷氨酸受体刺激有效地调制小电导钙激活钾（KCa2）通道。我们发现，神经元兴奋性毒性与谷氨酸暴露后3小时内KCa 2.2通道的快速下调有关。KCa 2通道的激活保留了KCa 2的表达，并显着减少了[Ca 2 +]i的病理性增加，在体外和体内提供了强大的神经保护作用。这些数据表明KCa2通道在兴奋性神经元细胞死亡中起关键作用，并提出其活化作为治疗急性和慢性神经退行性疾病的潜在治疗策略。
Exacerbated activation of glutamate receptor-coupled calcium channels and subsequent increase in intracellular calcium ([Ca2+]i) are established hallmarks of neuronal cell death in acute and chronic neurological diseases. Here we show that pathological [Ca2+]i deregulation occurring after glutamate receptor stimulation is effectively modulated by small conductance calcium-activated potassium (KCa2) channels. We found that neuronal excitotoxicity was associated with a rapid downregulation of KCa2.2 channels within 3 h after the onset of glutamate exposure. Activation of KCa2 channels preserved KCa2 expression and significantly reduced pathological increases in [Ca2+]i providing robust neuroprotection in vitro and in vivo. These data suggest a critical role for KCa2 channels in excitotoxic neuronal cell death and propose their activation as potential therapeutic strategy for the treatment of acute and chronic neurodegenerative disorders.
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DOI：
10.1085/jgp.200910295
发表时间：
2009-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Li W;Halling DB;Hall AW;Aldrich RW
通讯作者：
Aldrich RW
影响因子：
4.7
作者：
Chinopoulos, C;Gerencser, AA;Adam-Vizi, V
通讯作者：
Adam-Vizi, V
DOI：
10.1073/pnas.261323298
发表时间：
2001-12-18
影响因子：
11.1
作者：
Plesnila, N;Zinkel, S;Moskowitz, MA
通讯作者：
Moskowitz, MA
影响因子：
4.8
作者：
Sheng, Jian-zhong;Ella, Srikanth;Braun, Andrew P.
通讯作者：
Braun, Andrew P.
影响因子：
12.4
作者：
Landshamer, S.;Hoehn, M.;Culmsee, C.
通讯作者：
Culmsee, C.