Binding Sites on NMDA Receptor对NMDA受体的结合位点.ppt

Ligand-Gated Ion Channels General Features of LGICs Superfamilies of Ligand-Gated Channels Topologies for Ligand-Gated Ion Channels Cys-Loop Channels Topology of Cys-Loop Channels nAChR Subunit Composition nAChR: Single Channel Recording Structure of nAChR Ion Selection: Cationic Channels Model for nAChR Gating: Twisting of M2 Helices Atomic-Resolution Structure of nAChR GABA Receptor Subunit Composition Ion Selection: Chloride Channels GABA-R: Predicted Interaction Between Cys-Cys Loop and TM2-TM2 Linker Gating of GABA Channels: InteractionBetween the Cys-Loop and the M2-M3 Linker Crosslinking of Substituted Cysteinesin M2-M3 Link and Signature Loop Benzodiazepines and Barbiturates EnhanceGABAA Currents Through Different Mechanisms Ionotropic Glutamate Receptors Topology of Glutamate Receptors Ionotropic Glutamate Receptor Subunits Ion Selectivity of Glutamate Channels RNA Editing Determines Ca2+-Permeability of AMPA Receptors RNA Editing DeterminesCa2+-Permeability of AMPA Receptors Kinetics of Glutamate Channels Isolating AMPA-R and NMDA-R CurrentsWith Selective Blockers NMDA Receptors Bristle with Sites for Agonists and Modulators NMDAR Current: Voltage-Dependent Block by Mg2+ Mg2+ Site NMDA Receptors are ActivatedDuring Intense Synaptic Activity NMDA Receptors Mediate Synaptic Ca2+ Entry Synaptic Plasticity NMDA Receptors Induction of NMDAR-Dependent LTP LTP Requires a Transient NMDAR-Mediated Rise in Postsynaptic Ca2+ LTP (long-term potentiation): a stimulation-induced, persistent increase in synaptic efficiency Widely studied as a physiological model for memory formation and storage At many synapses, LTP involves postsynaptic NMDA receptors * Robert Blitzer, Ph.D. Depts. of Pharmacology and Psychiatry Mount Sinai School of Medicine Multimeric integral membrane glycoproteins Signal by D in membrane voltage or by Ca2+ entry Gating (opening after ligand binds) is very fast Central pore lined with a-helices Ion currents can be large Ion Selec