Review: Cav2.3 R-type Voltage-Gated Ca2+ Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity

Background: Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca 2+ channels are of central relevance in these processes. In particular, they are key elements in the etiopathogenesis of numerous seizure types and epilepsies. Earlier studies predominantly targeted on Ca v 2.1 P/Q-type and Ca v 3.2 T-type Ca 2+ channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Ca v 2.3 R-type Ca 2+ channel which exhibits an intriguing role in ictogenesis and seizure propagation. Ca v 2.3 R-type voltage gated Ca 2+ channels (VGCC) emerged to be important factors in the pathogenesis of absence epilepsy, human juvenile myoclonic epilepsy (JME), and cellular epileptiform activity, e.g . in CA1 neurons. They also serve as potential target for various antiepileptic drugs, such as lamotrigine and topiramate. Objective: This review provides a summary of structure, function and pharmacology of VGCCs and their fundamental role in cellular Ca 2+ homeostasis. We elaborate the unique modulatory properties of Ca v 2.3 R-type Ca 2+ channels and point to recent findings in the proictogenic and proneuroapoptotic role of Ca v 2.3 R-type VGCCs in generalized convulsive tonic–clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity. Conclusion: Development of novel Ca v 2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders.