Idiopathic epilepsies are genetically determined diseases of the central nervous system characterized by typical epileptic seizures and EEG abnormalities but not associated with structural brain lesions. In recent years, an increasing number of mutations associated with idiopathic epilepsy syndromes were identified in genes encoding subunits of voltageor ligand-gated ion channels. These encouraging results provide a plausible pathophysiological concept, since ion channels form the basis for neuronal excitability and are the major targets for anticonvulsive pharmacotherapy. The first epilepsy genes were identified for rare autosomal dominant syndromes within large pedigrees. Recently, a few mutations were also found for the frequent classical forms of idiopathic generalized epilepsies (IGE), for example absence or juvenile myoclonic epilepsy. The mutations can affect ion channels which on one hand have been known since several decades to be crucial for neuronal function, such as the voltage-gated sodium channel or the GABAA receptor, or on the other hand were newly identified within the last decade as KCNQ potassium channels or the ClC-2 chloride channel. Functional studies characterizing the molecular defects of the mutant channels point to a central role of GABAergic synaptic inhibition in the pathophysiology of IGE. Furthermore, newly discovered genes may be suitable as novel targets for pharmacotherapy such as KCNQ channels for the anticonvulsant drug retigabine. Altogether, these genetic and pathophysiological investigations will enhance our knowledge about the understanding of epileptogenesis and can help to improve anticonvulsive therapy.
Keywords: Ion channel, epilepsy, genetics, electrophysiology, patch clamp
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