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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,Ca~(2+)-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 Ca~(2+) 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 lowdose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca~(2+) and preventing neuronal apoptosis,and this is mediated by BK_(Ca) channel activation.
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, Ca ~ (2 (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 Ca ~ (2+) 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. These results indicate that low dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca ~ (2+) and preventing neuronal apoptosis, and this is mediated by BK_ (Ca) channel activation.