title: Correlation of AMPA receptor subunit composition with synaptic input in the mammalian cochlear nuclei.
abstract: The composition of AMPA receptors in patches excised from somata and dendrites of six cell types in the mammalian cochlear nuclei was probed and compared electrophysiologically and pharmacologically with the rapid application of glutamate. Cells excited predominantly by auditory nerve fibers had AMPA receptors with exceptionally rapid gating (submillisecond deactivation and desensitization time constants). The nonlinear current-voltage relationship in the presence of spermine showed that few of these receptors had GluR2 subunits, and the insensitivity of desensitization to cyclothiazide indicated that they contained mostly flop splice variants. At synapses made by parallel fibers, AMPA receptors were slowly gating (time constants of deactivation and desensitization >1 msec) and contained higher levels of GluR2 and flip isoforms. However, receptors at auditory nerve synapses on cells that also receive parallel fiber input, the fusiform cells, had intermediate properties with respect to kinetics and contained GluR2 and flip isoforms. Given the diverse biophysical properties, patterns of innervation, patterns of electrical activity, and targets of each cell type in vivo, these data indicate that the kinetics and permeation properties of AMPA receptors are linked to factors associated with synaptic connectivity.
authors.affiliation: Department of Physiology, University of Wisconsin Medical School-Madison, Madison, Wisconsin 53706, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Gardner
authors.forename: L O
authors.initials: LO
authors.lastname: Trussell
authors.forename: D
authors.initials: D
authors.lastname: Oertel
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001306:Auditory Pathways / Q000502:physiology; D001581:Benzothiadiazines / Q000494:pharmacology; D003056:Cochlear Nerve / Q000187:drug effects / Q000502:physiology*; D017626:Cochlear Nucleus / Q000187:drug effects / Q000502:physiology*; D004232:Diuretics; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D051379:Mice; D008813:Mice, Inbred ICR; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D018091:Receptors, AMPA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology; D013268:Stimulation, Chemical; D013395:Sucrose / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D001581:Benzothiadiazines; D004232:Diuretics; D018733:Nicotinic Antagonists; D020033:Protein Isoforms; D021122:Protein Subunits; D018091:Receptors, AMPA; D049993:Sodium Chloride Symporter Inhibitors; D018698:Glutamic Acid; D013395:Sucrose; C104722:glutamate receptor ionotropic, AMPA 2; C004639:cyclothiazide