抄録
Until recently, all genes found to be mutated in hereditary idiopathic epilepsies encoded subunits of ion channels or functionally related proteins, leading to the view of this class of diseases as channelopathies. Exceptions to this rule are the Mass1, the LGI1, and the EFHC1 genes. Mutations of the CHRNA4 and the CHRNB2 have been detected in families with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). To study pathogenesis of ADNFLE, a transgenic rat strains inserted a ADNFLE mutant CHRNA4 (S284L) has been developed. The KCNQ2 and KCNQ3 gene mutations were identified in families with benign familial neonatal convulsions (BFNC). The age-dependent development and spontaneous remission of BFNC reported to be associated with the functional switching of the GABAergic system from excitatory to inhibitory in neonatal CNS may be explained by the facts that NKCC1 (Cl-accumulating Na+, K+, -2C-, cotransporter) plays a pivotal role in the generation of GABA-mediated depolarization in immature cortical plate cells and KCC2 (Cl-extruding K+-Cl- cotransporter) promotes the later maturation of GABAergic inhibition in the rat neocortex. Mutations in the voltage-gated Na+-channel (VGSC:SCN1A, SCN2A, SCN1B) and GABAA receptor (GABRG2) genes have been identified in generalized epilepsy with febrile seizure plus (GEFS+), and those of SCN1A and GABRG2 in severe myoclonic epilepsy in infancy (SMEI), although GEFS+ and SMEI are clinically distinct from each other. The functional comsequences of these VGSC mutations remain controversial. Thus, functions should be analyzed not only in cells but in animal models such as S284L transgenic rat. [Jpn J Physiol 55 Suppl:S8 (2005)]
