Abstract
Tissue acidosis is a common feature of brain ischemia which causes neuronal injury. Activation of acid-sensing ion channel 1a (ASIC1a) plays an important role in acidosis-mediated neurotoxicity. Acute ethanol administration has been shown to provide neuroprotective effects during ischemic stroke, but the precise mechanisms have yet to be determined. In this study, we investigated the effect of ethanol on the activity/expression of ASIC1a channels and acidosis-induced neurotoxicity. We showed that acute treatment of neuronal cells with ethanol for more than 3 h could reduce ASIC1a protein expression, ASIC currents, and acid-induced [Ca2+]i elevation. We further demonstrated that ethanol-induced reduction of ASIC1a expression is mediated by autophagy-lysosome pathway (ALP)-dependent protein degradation. Finally, we showed that ethanol protected neuronal cells against acidosis-induced cytotoxicity, which effect was mimicked by autophagy activator rapamycin and abolished by autophagy inhibitor CQ. Together, these results indicate that moderate acute ethanol exposure can promote autophagy-lysosome pathway-dependent ASIC1a protein degradation and protect against acidosis-induced neurotoxicity.