Physiopathology of kainate receptors in epilepsy


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Abstract

HighlightsKainate receptors (KARs) regulate the activity of hippocampal networks.A role for KARs in chronic temporal lobe epilepsy (TLE) was discovered recently.In models of TLE, aberrant KARs operate at recurrent mossy fiber synapses.Aberrant synaptic GluK2-containing KARs contribute to chronic seizures in TLE.GluK2/GluK5 KARs constitute novel antiepileptic drug targets.Kainate receptors (KARs) are tetrameric ionotropic glutamate receptors composed of the combinations of five subunits GluK1–GluK5. KARs are structurally related to AMPA receptors but they serve quite distinct functions by regulating the activity of synaptic circuits at presynaptic and postsynaptic sites, through either ionotropic or metabotropic actions. Although kainate is a potent neurotoxin known to induce acute seizures through activation of KARs, the actual role of KARs in the clinically-relevant chronic phase of temporal lobe epilepsy (TLE) has long been elusive. Recent evidences have described pathophysiological mechanisms of heteromeric GluK2/GluK5 KARs in generating recurrent seizures in chronic epilepsy. The role of the other major subunit GluK1 in epileptogenic activity is still a matter of debate. This review will present the current knowledge on the subtype-specific pharmacology of KARs and highlight recent results linking KARs to epileptic conditions.

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