This section investigates excitatory amino acid receptor mechanisms in the vertebrate CNS, utilizing electrophysiological and molecular biological techniques. Fast perfusion systems are used for concentration jump application of agonists and antagonists to cells and membrane patches under voltage clamp; preparations in use include primary cultures of hippocampal neurons and glial progenitor cells, the CG-4 glial cell line, acutely dissociated sensory neurons, transfected cells and oocytes expressing recombinant receptors. Trapping of agonists at NMDA receptors during ion channel block by amino acridines was demonstrated using voltage jumps in agonist free solutions allowing blocked channels to open and conduct in the absence of agonist. Selectivity for allosteric modulation of the kainate and AMPA-preferring classes of non-NMDA receptors by concanavalin A and cyclothiazide was revealed using recombinant receptors, in conjunction with analysis of the response of native receptors in hippocampal and DRG neurons. In glial progenitors, analysis of the response to these modulators suggests coexpression of both families of glutamate receptors. Structure activity analysis for willardiine action at DRG and hippocampal neurons suggests a hydrophobic pocket in the agonist binding site for kainate but not AMPA receptors.
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