Nitric oxide/soluble guanylyl cyclase signaling mediates depolarization-induced protection of rat mesencephalic dopaminergic neurons from MPP+ cytotoxicity

► High K+ depolarization protects dopaminergic neurons from MPP+ cytotoxicity. ► The protective effect is dependent on nitric oxide and protein kinase G (PKG). ► 8-Nitro-cGMP is produced in response to high K+ depolarization. ► 8-Nitro-cGMP confers neuroprotection in a PKG-dependent manner. ► PKG-independent expression of heme oxygenase-1 is also involved in neuroprotection.