Ion channels and epilepsy

Abstract

Ion channels play a central role in the generation and control of neuronal excitability. Genetic defects in ion channels are associated with several forms of human idiopathic epilepsies. These defects range from nonsense and missense point mutations to insertion, truncation and splice site mutations producing altered, non‐functional or negative‐dominant channel subunits. To date, 12 mutated genes have been identified. They code for Na + ( SNC1A, SNC2A, SNC1B ), K + ( KCNA1, KCNQ2, KCNQ3 ) and Cl ‐ ( CLCN2 ) channel subunits, as well as neurotransmitter receptor subunits including Cl ‐ channel GABAA receptor ( GABRA1, GABRG2 ) and cationic channel acetylcholine receptor ( CHRNA4, CHRNB2 ). One ion transporter Na + /K + ATPase gene ( ATP1A2 ) has also been identified. The epilepsy syndromes related to these genes are as diverse as benign familial neonatal (BFNC ‐ KCNQ2 and 3 ) and infantile (BFNIC ‐ SNC2A and ATP1A2 ) convulsions, episodic ataxia with seizures (AE2 ‐ KCNA1 ), generalized epilepsy with febrile seizure plus (GEFS+ ‐ SCN2A, 1A, 1B and GABRG2 ), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE ‐ CHRNA4 and B2 ), severe myoclonic epilepsy of infancy (SMEI ‐ SNC1A ), juvenile myoclonic epilepsy (JME ‐ GABRA1 and CLCN2 ), and childhood and juvenile absence epilepsy (CAE, JAE ‐ SNC1B, GABRG2 and CLCN2 ). Despite the difficulty to correlate genotypes and phenotypes, these studies have increased our understanding of causal mechanisms of epilepsy and open a wide range of possibilities for developing better antiepileptic drugs and treatments.