title: Voltage-gated Ca(2+) channel mediated Ca(2+) influx in epileptogenesis.
abstract: Voltage- and ligand-gated ion channels are key elements in the etiopathogenesis of various forms of epilepsy. In this chapter, we present an overview of the functional implications of voltage-gated Ca(2+) channels in modulating internal Ca(2+) level fluctuations and generating ictiform/epileptiform cellular electrophysiological activity. A specific focus will be on the fascinating and evolving field of high-voltage activated (HVA) Non-L-type Ca(v)2.3 R-type channels and low-voltage activated (LVA) Ca(v)3.1-3.3 T-type Ca(2+) channels in the genesis of plateau potentials and excessive rebound bursting. Plateau potentials have been characterised in the hippocampus and were shown to be triggered by Ca(v)2.3 which subsequently activate CNG channels that mediate long-lasting plateaus. In the thalamocortical network, a complex ion channel armamentarium is involved in regulating a complex balance of burst and tonic mode activity. Recent findings point to an outstanding role of R- and T-type channels in both thalamocortical eurhythmia and pathophysiological -aberrations. Thus, pharmacological modulation of voltage-gated Ca(2+)-channels might prove more and more important in treatment of neurological and psychiatric disorder such as schizophrenia, mania, dementia and epilepsy.
authors.affiliation: Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany. magdalena.siwek@bfarm.de
authors.forename: Magdalena
authors.initials: M
authors.lastname: Siwek
authors.forename: Christina
authors.initials: C
authors.lastname: Henseler
authors.forename: Karl
authors.initials: K
authors.lastname: Broich
authors.forename: Anna
authors.initials: A
authors.lastname: Papazoglou
authors.forename: Marco
authors.initials: M
authors.lastname: Weiergräber
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D020908:Calcium Channels, R-Type / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000502:physiology; D027682:Cation Transport Proteins / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D006801:Humans
chemical_list: C423009:CACNA1E protein, human; C479952:CACNA1H protein, human; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D020747:Calcium Channels, T-Type; D027682:Cation Transport Proteins; D002118:Calcium