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This Article Full Text Full Text (PDF) All Versions of this Article: 97/5/3660    most recent 01193.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Weiergräber, M. Articles by Schneider, T. Search for Related Content PubMed PubMed Citation Articles by Weiergräber, M. Articles by Schneider, T.

Hippocampal Seizure Resistance and Reduced Neuronal Excitotoxicity in Mice Lacking the Ca_v2.3 E/R-Type Voltage-Gated Calcium Channel

¹Institute of Neurophysiology and ²Center of Molecular Medicine Cologne, University of Cologne, Cologne, Germany

Submitted 10 November 2006; accepted in final form 13 March 2007

Voltage-gated calcium channels are key components in the etiology and pathogenesis of epilepsies. Former studies mainly focused on P/Q-type Ca_v2.1 and T-type Ca_v3.2 Ca²⁺ channels involved in absence epileptogenesis, but recent findings also point to an intriguing role of the Ca_v2.3 E/R-type Ca²⁺ channel in ictogenesis and seizure propagation. Based on the observation that Ca_v2.3 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 Ca_v2.3^–/– mice compared with controls. In the present study we tested hippocampal seizure susceptibility in Ca_v2.3-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 Ca_v2.3^–/– mice compared with controls, whereas no difference in hippocampal EEG seizure activity between both genotypes could be detected at this suprathreshold dosage. The same tendency was observed for NMDA seizure susceptibility (150 mg/kg ip) approaching the level of significance. In addition, histochemical analysis within the hippocampus revealed that excitotoxic effects after kainic acid administration are absent in Ca_v2.3^–/– mice, whereas Ca_v2.3^+/+ animals exhibited clear and typical signs of excitotoxic cell death. These findings clearly indicate that the Ca_v2.3 voltage-gated calcium channel plays a crucial role in both hippocampal ictogenesis and seizure generalization and is of central importance in neuronal degeneration after excitotoxic events.