title: Ion channels and epilepsy.
abstract: Ion channels provide the basis for the regulation of excitability in the central nervous system and in other excitable tissues such as skeletal and heart muscle. Consequently, mutations in ion channel encoding genes are found in a variety of inherited diseases associated with hyper- or hypoexcitability of the affected tissue, the so-called 'channelopathies.' An increasing number of epileptic syndromes belongs to this group of rare disorders: Autosomal dominant nocturnal frontal lobe epilepsy is caused by mutations in a neuronal nicotinic acetylcholine receptor (affected genes: CHRNA4, CHRNB2), benign familial neonatal convulsions by mutations in potassium channels constituting the M-current (KCNQ2, KCNQ3), generalized epilepsy with febrile seizures plus by mutations in subunits of the voltage-gated sodium channel or the GABA(A) receptor (SCN1B, SCN1A, GABRG2), and episodic ataxia type 1-which is associated with epilepsy in a few patients--by mutations within another voltage-gated potassium channel (KCNA1). These rare disorders provide interesting models to study the etiology and pathophysiology of disturbed excitability in molecular detail. On the basis of genetic and electrophysiologic studies of the channelopathies, novel therapeutic strategies can be developed, as has been shown recently for the antiepileptic drug retigabine activating neuronal KCNQ potassium channels.
authors.affiliation: Department of Applied Physiology, Univeristy of Ulm, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Lerche
authors.forename: K
authors.initials: K
authors.lastname: Jurkat-Rott
authors.forename: F
authors.initials: F
authors.lastname: Lehmann-Horn
mesh_terms: D001259:Ataxia / Q000235:genetics / Q000378:metabolism; D004831:Epilepsies, Myoclonic / Q000235:genetics / Q000378:metabolism; D004828:Epilepsies, Partial / Q000235:genetics / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D020936:Epilepsy, Benign Neonatal / Q000235:genetics / Q000378:metabolism; D017034:Epilepsy, Frontal Lobe / Q000235:genetics / Q000378:metabolism; D004829:Epilepsy, Generalized / Q000235:genetics / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D020385:Myokymia / Q000235:genetics / Q000378:metabolism; D003294:Seizures, Febrile / Q000235:genetics / Q000378:metabolism
chemical_list: D007473:Ion Channels