The Cav2.3 voltage-gated calcium channel in epileptogenesis—Shedding new light on an enigmatic channel

The Cav2.3 encoded Ca2+ channel is probably one of the least well-understood voltage-gated calcium channels in terms of physiology, pharmacology and clinical relevance. Here we provide a detailed insight into the functional involvement of Cav2.3 in etiology and pathogenesis of both convulsive and non-convulsive seizures. In the CNS, Cav2.3 containing E/R-type Ca2+ channels are involved in triggering epileptiform discharges by significantly contributing to plateau potentials and afterdepolarisations. Pharmacological analysis further revealed that various antiepileptic drugs specifically target Cav2.3 VGCCs capable of blocking epileptiform burst activity. Whereas electroencephalographic recordings in Cav2.3−/− mice did not reveal any ictal-like discharges, seizure susceptibility was dramatically reduced in Cav2.3−/− animals compared to controls, further supporting the observation that Cav2.3 is an important factor in triggering epileptiform activity in neuronal populations. Although some aspects of its relationship to epilepsy have been uncovered, further functional characterization of Cav2.3 in etiology and pathogenesis of human epileptic syndromes as well as development of new antiepileptic drugs specifically targeting Cav2.3 turns out to become indispensable.