Gating and permeation of kainate receptors: differences unveiled

Abstract

Kainate receptors (KARs) represent, together with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl D-aspartate (NMDA) receptors, one of the three families of ionotropic glutamate receptors. Recent advances in the study of their biophysical properties have revealed a surprising diversity. KAR-mediated excitatory postsynaptic currents (EPSCs) are often much slower than AMPA receptor-mediated EPSCs, and this is probably due to the slow deactivation rate of KARs containing the GluK4 or GluK5 subunits. By contrast, GluK3-containing receptors, unlike other AMPA/kainate receptors, desensitize faster at low agonist concentrations, making these receptors insensitive to glutamate spillover from neighboring synapses. Moreover, KARs have a wide range of sensitivities to intracellular polyamines and consequently of voltage dependent activation. Finally, newly discovered associated proteins, such as Neto1 and 2, have marked effects on receptor properties, increasing further the potential diversity of KAR functional properties. Altogether, this functional diversity of KARs could have profound consequences on their ability to shape synaptic transmission under physiological and pathological conditions.