Hippocampal Seizure Resistance and Reduced Neuronal Excitotoxicity in Mice Lacking the Cav2.3 E/R-Type Voltage-Gated Calcium Channel

Voltage-gated calcium channels are key components in the etiology and pathogenesis of epilepsies. Former studies mainly focused on P/Q-type Cav2.1 and T-type Cav3.2 Ca2+ channels involved in absence epileptogenesis, but recent findings also point to an intriguing role of the Cav2.3 E/R-type Ca2+ channel in ictogenesis and seizure propagation. Based on the observation that Cav2.3 is thought to induce plateau potentials in CA1 pyramidal cells, which can trigger epileptiform activity, our recent investigation revealed reduced PTZ-seizure susceptibility and altered seizure architecture in Cav2.3−/− mice compared with controls. In the present study we tested hippocampal seizure susceptibility in Cav2.3-deficient mice using surface and deep intrahippocampal telemetric EEG recordings as well as phenotypic seizure video analysis. Administration of kainic acid (30 mg/kg ip) revealed clear alteration in behavioral seizure architecture and dramatic resistance to limbic seizures in Cav2.3−/− mice compared with contro...