1 Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China
2 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
3 Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing 100050, China
4 Beijing Institute for Brain Disorders, Beijing 100069, China
5 China National Clinical Research Center for Neurological Diseases, Beijing 100050, China

Abstract 

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 (BKCa) 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 BKCa channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BKCa 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 BKCa channel activation.

Keywords

Oxygen-glucose deprivation/reoxygenation, Ethanol preconditioning, BKCa channel, Neuroprotection, Apoptosis

[SpringerLink]