Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 3 Pasteur St., 02-093 Warsaw, Poland.
Mitochondrion. 2012 Jan;12(1):169-72. doi: 10.1016/j.mito.2011.12.001. Epub 2012 Jan 5.
In the present study, we show that the large conductance calcium-activated potassium channel (BK(Ca) channel) inhibitor paxilline protects neuronal cells against glutamate-induced cell death. In our studies, we used HT22 mouse hippocampal cells as an experimental model and observed that the effect of paxilline was dose-dependent. We also found that other inhibitors of BK(Ca) channels, iberiotoxin and charybdotoxin, were not cytoprotective. Paxillinol, which is a structural analog of paxilline but does not inhibit BK(Ca) channel, also protected HT22 cells against glutamate-induced toxicity. These data suggest that the observed cytoprotection was not related to BK(Ca) channel inhibition by paxilline. In addition, paxilline neither restored glutathione levels nor reduced the amount of reactive oxygen species upon glutamate treatment. Our results suggest that paxilline protects neuronal HT22 cells against glutamate-induced cell death independently of BK(Ca) channel activity and oxidative stress induced by glutamate treatment.
在本研究中，我们表明大电导钙激活钾通道（BK(Ca) 通道）抑制剂巴卡丁 III 可保护神经元细胞免受谷氨酸诱导的细胞死亡。在我们的研究中，我们使用 HT22 小鼠海马细胞作为实验模型，观察到巴卡丁 III 的作用具有剂量依赖性。我们还发现，BK(Ca) 通道的其他抑制剂，iberiotoxin 和 charybdotoxin，没有细胞保护作用。巴卡丁醇是巴卡丁 III 的结构类似物，但不抑制 BK(Ca) 通道，也能保护 HT22 细胞免受谷氨酸诱导的毒性。这些数据表明，观察到的细胞保护作用与巴卡丁 III 对 BK(Ca) 通道的抑制无关。此外，巴卡丁 III 既不能恢复谷胱甘肽水平，也不能减少谷氨酸处理后活性氧物质的含量。我们的结果表明，巴卡丁 III 可保护神经元 HT22 细胞免受谷氨酸诱导的细胞死亡，与 BK(Ca) 通道活性以及谷氨酸处理诱导的氧化应激无关。
