Glutamate Receptor Channels, RNA Editing, and Epilepsy

Abstract

In the mammalian central nervous system (CNS) fast excitatory neurotransmission is mediated by ionotropic glutamate receptors (GluRs) of the AMPA/kainate and NMDA receptor families (Collingridge and Lester 1989; Mayer and Westbrook 1987; Watkins et al. 1990). The AMPA receptors mediate the fast component of excitatory postsynaptic currents, whereas the slow component is contributed by NMDA receptors (e.g., Stern et al. 1992). The latter can be viewed as coincidence detectors of pre- and postsynaptic activity, since the gating of the integral ion channel requires two closely simultaneous events, presynaptic release of glutamate and depolarization of the postsynaptic membrane. Depolarization is induced primarily by the activation of synaptically colocalized AMPA receptors. Coincidence detection by the NMDA receptor rests on its voltage-dependent channel block by extracellular Mg2+. NMDA receptors are designed for high Ca2+ permeability, and Ca2+ influx through the NMDA receptor channel is thought to be essential for activity-dependent synaptic modulation (reviewed in Bliss and Collingridge 1993). Furthermore, excessively high Ca2+ influx through NMDA receptors has pathophysiological consequences, including epileptiform activities and neurodegeneration (Choi 1988). By contrast, Mg2+. NMDA receptors are designed for high Ca2+ permeability, and Ca2+ influx through the NMDA receptor channel is thought to be essential for activitydependent synaptic modulation (reviewed in Bliss and Collingridge 1993). Furthermore, excessively high Ca2+ influx through NMDA receptors has pathophysiological consequences, including epileptiform activities and neurodegeneration (Choi 1988).