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  • Title: [Ion channels and epilepsy].
    Author: Armijo JA, de las Cuevas I, Adín J.
    Journal: Rev Neurol; 2000 Jun; 30 Suppl 1():S25-41. PubMed ID: 10904966.
    Abstract:
    OBJECTIVE: We review the role of ligand-gated ion channels and voltage-gated ion channels as a substrate for the epileptogenesis and as targets in the development of new antiepileptic drugs. DEVELOPMENT: Voltage-gated calcium channels are involved in the release of neurotransmitters, in the sustained depolarization-phase of paroxysmal depolarisation shifts (PDS), and in the generation of absences; they are also the genetic substrate of generalized tonic-clonic convulsions and absence-like pattern seen in some mice. The voltage-gated potassium channel has been implicated in the hyperpolarization-phase of PDS, it is the genetic substrate of the long QT syndrome, benign neonatal epilepsy, and episodic ataxia/myokymia syndrome, and it is the target of some antiepileptic drugs which activate this channel. The voltage-gated sodium channel is the target of most of the classical and newer antiepileptic drugs; it is also the substrate for generalized epilepsy with febrile seizures plus. The sodium channel of the nicotinic acetylcholine receptor is the substrate for nocturnal frontal lobe epilepsy. The sodium channels of the AMPA and KA glutamate receptors have been proposed as substrate for juvenile absence epilepsy and are a target for new antiepileptic drugs which inhibit it. The calcium channel of the NMDA glutamate receptor has been implicated in the sustained depolarization-phase of PDS and in epileptogenesis after kindling and is a main target for new antiglutamate drugs. The chloride channel of the GABAA receptor is responsible for the rapid hyperpolarization of PDS, it has been involved in epileptogenesis after kindling, it may be the substrate of the Angelman syndrome, and it is activated by many classical and new antiepileptic drugs. CONCLUSION: The knowledge of the role of the ion channels in the epilepsies is allowing the design of new and more specific therapeutic strategies.
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