Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca²⁺-Activated K⁺ Channels In Vitro

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• 作者：Fang Su ; An-Chen Guo ; Wei-Wei Li ; Yi-Long Zhao ; Zheng-Yi Qu…
• 关键词：Oxygen ; glucose deprivation/reoxygenation ; Ethanol preconditioning ; BKCa channel ; Neuroprotection ; Apoptosis
• 刊名：Neuroscience Bulletin
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：33
• 期：1
• 页码：28-40
• 全文大小：
• 刊物主题：Neurosciences; Human Physiology; Anesthesiology; Anatomy; Neurology; Pain Medicine;
• 出版者：Springer Singapore
• ISSN：1995-8218
• 卷排序：33

文摘

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca2+-activated K+ channel (BK_Ca) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BK_Ca channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BK_Ca channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca2+ and preventing neuronal apoptosis, and this is mediated by BK_Ca channel activation.