title: The role of calcium channel mutations in human epilepsy.
abstract: Molecular insights into monogenic idiopathic epilepsies have illustrated the central role of channelopathies in their etiology. Among ion channels, both high- and low-voltage-activated calcium channels and their ancillary subunits Cav2.1 (P/Q-type) calcium channels support a number of dynamic processes in neurons at both presynaptic and postsynaptic levels being critical determinants of neuronal excitability. Therefore, their alterations in the expression or biophysical properties may have a central role in the pathogenesis of epilepsy phenotypes. Indeed, low-voltage-activated (T-type) calcium channels are critically involved in normal burst firing in the thalamocortical circuitry recruited in the spike-wave discharges underlying absence seizures. Moreover, gain-of-function mutations have been identified in several calcium channel genes in both epilepsy patients and animal models of epilepsy, further underpinning the role of calcium channels in epilepsy pathophysiology. Thus, the selective pharmacological blockade of calcium channel subtypes may provide attractive targets for the development of antiepileptic therapies.
authors.affiliation: Institute of Neurology, Department of Medical Sciences, University Magna Graecia, Catanzaro, Italy. Electronic address: a.gambardella@unicz.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: Institute of Neurology, Department of Medical Sciences, University Magna Graecia, Catanzaro, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Labate
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D009154:Mutation
chemical_list: D015220:Calcium Channels
keywords: P/Q-type channels; T-type channels; calcium channel; epilepsy; seizures