There are three glutamate receptor superfamilies defined by the specific agonist binding to them - NMDA, AMPA and kainate.

Several types of kainate receptors have been cloned and classified. Two of these have a high affinity to kainate (GLUK1 and GLUK2), while GLUK5, as well as other members of the family, have a lower affinity¹. GLUK5, GLUK6 and GLUK7 have a 75-80% identical amino acid sequence making them a separate subfamily from the other kainate receptors.

The GLUK5 receptor, similar to its subfamily members, is a ligand-gated ion channel. It has an extracellular N-terminus comprised of eight glycosylation consensus sites, four transmembrane domains arranged in a three-plus-one pattern with a large intracellular domain between units three and four and a C-terminus². GLUK5 is expressed in DRG neuron cell bodies where currents in these cells are preferentially induced by kainate and not AMPA³ and also in trigeminal neurons where kainate receptor antagonists are effective in a dural plasma protein extravasation model of migraine in rats⁴.

Little is known about the role of GLUK5 in pathologies. A study examining the role of the receptor in brain pathology using GLUK5 antagonists on hippocampal cells slices, found that blocking of the kainate receptor prevents the development of epileptic activity evoked by muscarinic antagonist. The administration of GLUK5 antagonists to conscious mice in the same study showed that the antagonist prevents limbic seizures induced by hippocampal pilocarpine perfusion without evident side effects. These findings suggest that GLUK5 antagonists may be effective in the treatment of epilepsy and further research in this field is required⁵.