A glutamate receptor channel with high affinity for domoate and kainate.
The non-NMDA family of glutamate receptors comprises a growing number of structurally related subunits (GluR-A to -D or -1 to -4; GluR-5, -6; KA-1). GluR-A to -D appear to constitute the major AMPA receptor subtypes but the functional and pharmacological characteristics of the other subunits are unresolved. Using a mammalian expression system we demonstrate here that homomeric GluR-5 receptors exhibit properties of a high affinity domoate (KD approximately 2 nM) and kainate (KD approximately 70 nM) binding site. For these receptors, the rank order of ligands competing with [3H]kainate binding was domoate much greater than quisqualate approximately glutamate much greater than AMPA approximately CNQX. The respective receptor channels were gated in decreasing order of sensitivity by domoate, kainate, glutamate and AMPA. In contrast to recombinantly expressed GluR-A to -D channels, currents elicited at GluR-5 receptor desensitize channels to all agonists. This property is characteristic of currents in peripheral neurons on sensory ganglia. These findings suggest the existence of at least two distinct types of non-NMDA receptor channels, both gated by AMPA and kainate, but differing in pharmacology and current properties.
Laboratory of Molecular Neuroendocrinology, Heidelberg University, FRG.
B
B
Sommer
N
N
Burnashev
T A
TA
Verdoorn
K
K
Keinänen
B
B
Sakmann
P H
PH
Seeburg
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D004594:Electrophysiology / Q000379:methods; D005971:Glutamates / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D016548:Prosencephalon / Q000502:physiology*; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D005971:Glutamates; D007473:Ion Channels; D046911:Macromolecular Substances; D009498:Neurotoxins; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C012301:domoic acid; D007608:Kainic Acid