Zhao, Q; (2013) Activation properties and pharmacology of NMDA receptors in rat Substantia Nigra. Doctoral thesis (PhD), UCL (University College London).

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Abstract

In this thesis i have used patch-clamp single channel and whole-cell recordings to quantify the properties of NMDA receptors in pars compacta of the substania nigra (SNc) dopaminergic neurons. NMDA receptors are ubiquitously expressed in the central nervous system and are generally composed of two glycine-binding GIuN1 subunits and two glutamate binding GIuN2 subunits. While many receptors are diheteromers of GluN1 and a single type of GiuN2 subunit, there is evidence for triheteromeric GIuN1/GIuN2B/GIuN2D receptors in the midbrain and cerebellum. Results suggest NMDA receptor activation in SNc dopaminergic neurons produces bursts of channel openings, which combined with the first latencies to activation, generate the familiar slowly rising and decaying macroscopic NMDA response. A modification to a standard kinetic model of NMDA receptor activation (the Banke & Traynelis model) was found to adequately fit the low NMDA concentration single channel data and the rate constants from this fitting predicted a macroscopic response to a brief pulse of 1 mM NMDA that was similar to that observed in concentration jump experiments. The co-localization of kinetically distinct GIuN2B and GIuN2D subunits in a single triheteromeric GluN1/GluN2B/GiuN2D receptor may account for the combination of pharmacological and kinetic properties observed in these experiments for NMDA receptors from the rat substantia nigra.

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