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Contrasting molecular composition and channel properties of AMPA receptors on chick auditory and brainstem motor neurons.

Abstract
1. Neurons in the brainstem auditory pathway exhibit a number of specializations for transmitting signals reliably at high rates, notably synaptic AMPA receptors with very rapid kinetics. Previous work has not revealed a common structural pattern shared by the AMPA receptors of auditory neurons that could account for their distinct functional properties. 2. We have used whole-cell patch-clamp recordings, mRNA analysis, immunofluorescence, Western blots and agonist-evoked cobalt uptake to compare AMPA receptors on the first-, second- and third-order neurons in the chick ascending auditory pathway with those on brainstem motor neurons of the glossopharyngeal/vagal nucleus, which have been shown to have very slow desensitization kinetics. 3. The results indicate that the AMPA receptors of the cochlear ganglion, nucleus magnocellularis and nucleus laminaris share a number of structural and functional properties that distinguish them from the AMPA receptors of brainstem motor neurons, namely a lower relative abundance of glutamate receptor (GluR)2 transcript and much lower levels of GluR2 immunoreactivity, higher relative levels of GluR3 flop and GluR4 flop, lower relative abundance of the C-terminal splice variants GluR4c and 4d, less R/G editing of GluR2 and 3, greater permeability to calcium, predominantly inwardly rectifying I-V relationships, and greater susceptibility to block by Joro spider toxin. 4. We conclude that the AMPA receptors of auditory neurons acquire rapid kinetics from their high content of GluR3 flop and GluR4 flop subunits and their high permeability to Ca2+ from selective post-transcriptional suppression of GluR2 expression.
AuthorsA Ravindranathan, S D Donevan, S G Sugden, A Greig, M S Rao, T N Parks
JournalThe Journal of physiology (J Physiol) Vol. 523 Pt 3 Pg. 667-84 (Mar 15 2000) ISSN: 0022-3751 [Print] England
PMID10718746 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • JSTX spider toxin
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, AMPA
  • Spider Venoms
  • glutamate receptor ionotropic, AMPA 4
  • Cobalt
  • glutamate receptor ionotropic, AMPA 2
  • Calcium
Topics
  • Animals
  • Auditory Pathways (cytology, metabolism)
  • Blotting, Western
  • Brain Stem (cytology, metabolism)
  • Calcium (metabolism)
  • Chick Embryo
  • Cobalt (pharmacokinetics)
  • Fluorescent Antibody Technique
  • Motor Neurons (metabolism)
  • Neurons (metabolism)
  • Patch-Clamp Techniques
  • Protein Isoforms (genetics)
  • RNA Editing
  • RNA, Messenger (metabolism)
  • Receptors, AMPA (antagonists & inhibitors, genetics, metabolism, physiology)
  • Spider Venoms (pharmacology)

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