Single-Channel Studies of Glutamate Receptors

Publisher Summary The first impression that arises from a survey of the properties of glutamate receptor (GluR) is one of diversity; however, there may be unifying themes underlying the diversity. To identify such themes, it is necessary to focus on the excitatory D-GluR as there is inadequate evidence concerning the anion-selective GluR for any consistent picture of the latter to emerge. A range of different cation selectivities and single-channel conductances emerge when the D-GluRs of invertebrates and of mammals are compared. A detailed comparison of gating kinetics of invertebrate and mammalian D-GluR is not yet possible. However, some evidence for state-switching of N -methyl- d -aspartate–sensitive receptor (NMDA-R) kinetics has been reported. Such state-switching is characteristic of the locust D -GluR when desensitization is blocked by concanavalin A. The main evidence for a close relationship among different GluRs comes from pharmacological studies. Thus, the D -GluR of insect and crustacean muscle and one of the mammalian central nervous system (CNS) GluR are selective for quisqualate as an agonist. Therefore, the agonist-binding sites of these GluRs are structurally similar. Studies of noncompetitive antagonism of GluR by polyamine toxins suggest that there are similarities between the structures of the ionophoric regions of D-GluR of arthropod muscle and NMDA-R of mammalian CNS. The naturally occurring polyamine toxins and their synthetic analogs may well be important tools for probing the subtleties of this relationship. The polyamine toxins also block cation-selective channels gated by other types of receptors (e.g., the nicotinic acetylcholine receptor), albeit with higher dissociation constants than those for antagonism of GluR. A further indication of an underlying unity in the properties of GluR comes from studies of inhibition of receptor desensitization by concanavalin A. This has been shown for several invertebrate D-GluR and for the quisqualate-sensitive receptor (Quis-R) of the mammalian CNS.