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NMDA receptors: linking physiological output to biophysical operation

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Introduction

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  • NMDA is part of the iGluR family, aside AMPA and kainate receptors, and have largely a similar structure
  • AMPA determine the onset and maximal amplitude of the EPSC. NMDA, given its slow gating, determines the decay of the EPSC
  • Molecular composition of native NMDARs is yet undefined

Observing the NMDAR output

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  • NMDARs are heterotetramers of seven genetically encoded, differentially expresssed subunits:
    • GluN1 (8 different variants produced by splicing)
    • 4 GluN2 (GluN2A-D)
    • 2 GluN3 (GluN3B)
  • Glutamatergic NMDARs contain at least one GluN1 (co-agonist glycine binding site) subunit and at least one GluN2 subunit (glutamate binding site).
  • Additional diversity of function (kinetics, voltage dependency of block,Ca2+ cond.) is conferred by further composition