Nicorandil prevents oxidative stress-induced apoptosis in neurons by activating mitochondrial ATP-sensitive potassium channels

Nicorandil, a clinically useful drug for the treatment of ischemic heart disease, has an anti-apoptotic effect in cardiomyocytes, and activation of mitochondrial ATP-sensitive potassium (mitoK_ATP) channels underlies this effect. Recently, several studies showed that nicorandil reduced brain injury in animal models of brain ischemia. Based on these facts, we hypothesized that nicorandil may have anti-apoptotic effects in neurons mediated by mitoK_ATP channels. We investigated the effect of nicorandil on apoptosis induced by oxidative stress using cultured cerebellar granule neurons. Nicorandil (100 μmol/l) significantly suppressed the number of cells with TUNEL-positive nuclei and the increase in caspase-3 activity induced by 20 μmol/l H₂O₂. An indicator dye for mitochondrial inner membrane potential (ΔΨ_m) revealed that nicorandil prevented the loss of ΔΨ_m induced by H ₂O₂ in a concentration-dependent manner. These effects were abolished by 5-hydroxydecanoate (5HD; 500 μmol/l), a mitoK _ATP channel blocker. The present results showed that nicorandil has anti-apoptotic effects in neurons, at least in part, by preserving ΔΨ_m.