Kainate receptors in epilepsy and excitotoxicity

Abstract

Kainate (KA), an analog of glutamate, is a potent neurotoxin that has long been known to induce behavioral and electrophysiological seizures as well as neuropathological lesions reminiscent of those found in patients with temporal lobe epilepsy. More than a decade after the initial KA studies, molecular cloning of ionotropic glutamate receptors identified a family of receptors that binds KA with high affinity. The present review explores the links between the epileptogenic and excitotoxic actions of KA and the function of kainate receptors (KARs) in the activity of neuronal networks. We first present evidence that KARs are the main targets of KA to produce the epileptogenic and excitotoxic effects of KA and KA analogs, and we discuss the mechanisms of action of KA. Then the review evaluates the involvement of KARs activated by the endogenous agonist glutamate in the generation and propagation of epileptiform activity. Finally, we report recent findings proposing KARs as targets of antiepileptic drugs and neuroprotective agents.