BKCa channel is a molecular target of vitamin C to protect against ischemic brain stroke.

Abstract

Epidemiological studies have demonstrated that vitamin C decreases the risk of stroke, which has generally been ascribed to its function as antioxidant and free radical scavenger. However, whether there is a defined molecular target for vitamin C on stroke is unknown. Utilizing middle cerebral artery occlusion (MCAO) in rats as a model for ischemic stroke, we demonstrated that long-term, low-dose administration of vitamin C prior to MCAO could exert significant neuroprotective effect on the brain damage. The long-term, low-dose vitamin C pretreated rats had decreased brain infarct size and decreased neurological deficit score compared with the vehicle or single high dose pretreated MCAO rats. Furthermore, electrophysiological experiments using patch clamp technique showed that vitamin C increased the whole-cell current of the large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel. Moreover, vitamin C increased the open probability of the channel without change its amplitude. Importantly, blockade of the BK_Ca channels abolished the neuroprotective effect of vitamin C on MCAO. Therefore, this study shows that long-term, low-dose pretreatment with vitamin C could reduce MCAO-induced brain damage through activation of the BK_Ca channels, suggesting that the BK_Ca channel is a molecular target of vitamin C on stroke.