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The Journal of Neuroscience, May 1, 2002, 22(9):3392-3403
Functional Stoichiometry of Glutamate Receptor Desensitization
Derek Bowie1 and G. David Lange2 1 Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, and 2 Instrumentation and Computer Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
Potassium (K+) channels and ionotropic glutamate receptors (iGluRs) fulfill divergent roles in vertebrate nervous systems. Despite this, however, recent work suggests that these ion channels are structurally homologous, sharing an ancestral protein, architectural design, and tetrameric subunit stoichiometry. Their gating mechanisms also are speculated to have overlapping features. Here we show that the mechanism of iGluR desensitization is unique. Unlike K+ channels, AMPA- and kainate-type iGluR subunits desensitize in several ordered conformational steps. AMPA receptors operate as dimers, whereas the functional stoichiometry of kainate receptor desensitization is dependent on external ions. Contrary to conventional understanding, kinetic models suggest that partially desensitized AMPA and kainate receptors conduct ions and are likely participants in synaptic signaling. Although sharing many structural correlates with K+ channels, iGluRs have evolved unique subunit-subunit interactions, tailoring their gating behavior to fulfill distinct roles in neuronal signaling.
Key words: glutamate; AMPA; kainate; desensitization; stoichiometry; gating
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293392-12$05.00/0
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