GluK

GluK refers to a family of kainate receptor subunits that form part of the ionotropic glutamate receptor family. In humans, the GluK subunits are encoded by the GRIK1-GRIK5 genes and include GluK1 (GRIK1), GluK2 (GRIK2), GluK3 (GRIK3), GluK4 (GRIK4, also known as KA1), and GluK5 (GRIK5, also known as KA2). The term GluK may denote the individual subunits or the kainate receptor complexes they assemble into.

Structure and assembly: Kainate receptors are tetrameric ligand-gated ion channels. Subunits can assemble as homo- or heteromers, giving rise to diverse pharmacology and kinetic properties. Each subunit contributes to the extracellular ligand-binding domain that binds glutamate-like agonists and to the transmembrane domain that forms the ion channel pore. Receptor desensitization and post-translational modifications influence trafficking, localization, and function, while KA1 and KA2 subunits modulate receptor assembly and pharmacology when incorporated into heteromeric receptors.

Expression and function: KARs are widely expressed in the central nervous system, with notable presence in the hippocampus, cortex, and thalamus, though regional patterns vary. They can be located postsynaptically, mediating fast excitatory currents, and presynaptically, where they modulate neurotransmitter release and regulate synaptic transmission and plasticity. Activation generally permits Na+ and K+ flux, and Ca2+ permeability depends on subunit composition, contributing to diverse intracellular signaling and synaptic dynamics.

Pharmacology and clinical significance: KARs are activated by kainic acid and domoic acid; antagonists such as NBQX block kainate receptors as well as AMPA receptors. Subunit-selective modulators are under investigation. KARs have been linked to epilepsy, ischemic injury, neuropathic pain, and some neuropsychiatric conditions, making them potential targets for therapeutic intervention while presenting challenges due to receptor heterogeneity and trafficking.