Role of Ca(v) 2.3 (alpha1E ) Ca2+ channel in ischemic neuronal injury

We investigated the role of the Ca(v)2.3 (alpha1E) channel in ischemic neuronal injury using Ca(v)2.3 mutant mice. In focal ischemia model with a complete occlusion of the middle cerebral artery in vivo, infarct at 24 h was significantly larger in Ca(v)2.3 mutant mice compared with that in wild-type controls. In vitro Ca2+ imaging studies using hippocampal slices revealed that oxygen-glucose deprivation induced a [Ca2+]i increase in the hippocampal CA1 region more vigorously in Ca(v)2.3 mutant mice than in wild-type controls, and that tetrodotoxin or bicuculline application abolished the difference between the genotypes. These results suggest that the Ca(v)2.3 channel plays a protective role in ischemic neuronal injury by a mechanism in which GABAergic neuronal actions are involved.