Cav2.3- and Cav3.2-deficient mice both display seizure resistance in the kainic acid model of epilepsy

Divalent heavy metal cations (Ni²⁺, Zn²⁺) antagonize the activity of voltage-gated Ca²⁺ channels. Ca_v2.3 (R-type) and Ca_v3.2 (one of three T-type) channels are most sensitive towards Ni²⁺ (IC₅₀ at 10 – 12 µM) and Zn²⁺ (IC₅₀ at 3 µM (Kang et al. 2009)). Both channel types contribute to experimentally induced epilepsy either by kainate (20 – 30 mg/kg i.p.) for Ca_v2.3 (after 24 hours) or by pilocarpine (330 mg/kg s.c.) for Ca_v3.2 (after 48 hours) (Weiergräber et al. 2007; Becker et al. 2008). In both systems hippocampal neurodegeneration was even prevented by gene inactivation of the ion conducting subunit. To understand the mechanism of kainate-induced epilepsy in greater detail, we compared the effects of kainic acid injection in Ca_v3.2-deficient mice with Ca_v2.3-KO’s and control mice side-by-side. We show that ablation of either Cav3.2 or Cav2.3 produces two different seizure resistant phenotypes with different neuroprotective capacities. These findings may point toward a synergistic mode of action of both of these calcium channels in epileptogenesis.