Ion channels and epilepsy

Ion channels provide the basis for the regulation of excitability in the ce ntral nervous system and in other excitable tissues such as skeletal and he art muscle. Consequently, mutations in ion channel encoding genes are found in a variety of inherited diseases associated with hyper- or hypoexcitabil ity of the affected tissue, the so-called 'channelopathies.' An increasing number of epileptic syndromes belongs to this group of rare disorders: Auto somal 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 co nstituting the M-current (KCNQ2, KCNQ3), generalized epilepsy with febrile seizures plus by mutations in subunits of the voltage-gated sodium channel or the GABAA receptor (SCN1B, SCN1A GABRG2), and episodic ataxia type 1-whi ch is associated with epilepsy in a few patients-by mutations within anothe r voltage-gated potassium channel (KCNA1). These rare disorders provide int eresting models to study the etiology and pathophysiology of disturbed exci tability in molecular detail. On the basis of genetic and electrophysiologi c studies of the channelopathies, novel therapeutic strategies can be devel oped, as has been shown recently for the antiepileptic drug retigabine acti vating neuronal KCNQ potassium channels. (C) 2001 Wiley-Liss, Inc.