title: Review: Cav2.3 R-type Voltage-Gated Ca2+Channels - Functional Implications in Convulsive and Non-convulsive Seizure Activity.
abstract: BACKGROUND
  Researchers have gained substantial insight into mechanisms of synaptic transmission, hyperexcitability, excitotoxicity and neurodegeneration within the last decades. Voltage-gated Ca2+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 Cav2.1 P/Q-type and Cav3.2 T-type Ca2+channels relevant for absence epileptogenesis. Recent findings bring other channels entities more into focus such as the Cav2.3 R-type Ca2+channel which exhibits an intriguing role in ictogenesis and seizure propagation. Cav2.3 R-type voltage gated Ca2+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 Ca2+homeostasis. We elaborate the unique modulatory properties of Cav2.3 R-type Ca2+channels and point to recent findings in the proictogenic and proneuroapoptotic role of Cav2.3 R-type VGCCs in generalized convulsive tonic-clonic and complex-partial hippocampal seizures and its role in non-convulsive absence like seizure activity.
  
  
  CONCLUSIONS
  Development of novel Cav2.3 specific modulators can be effective in the pharmacological treatment of epilepsies and other neurological disorders.
authors.affiliation: Department of Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Wormuth
authors.affiliation: Department of Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lundt
authors.affiliation: Department of Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Henseler
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Cologne, Faculty of Medicine, Cologne, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Broich
authors.affiliation: Department of Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Papazoglou
authors.affiliation: Department of Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Weiergräber
keywords: Absence epilepsy; Afterdepolarisation; Ictal discharges; Low-threshold Ca2+ spike; Plateau potentials; R-type; Seizure