NMDA Receptors: Structure and Function
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NMDA Receptors: Structure and Function

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What is the function of the M2 helix in ionotropic receptors?

  • It transmits electrical signals to adjacent neurons.
  • It interacts with neurotransmitters.
  • It binds to receptor oligomers.
  • It lines the channel pore. (correct)

    • Which of the following receptors is categorized under ionotropic receptors?

  • Beta-adrenergic receptor
  • GABAA receptor (correct)
  • Dopamine D2 receptor
  • Muscarinic acetylcholine receptor

    • What is the typical size of the protrusions representing AChR oligomers in the postsynaptic membrane of the Torpedo electric organ?

  • 8 to 9 nm (correct)
  • 7 to 8 nm
  • 5 to 6 nm
  • 10 to 11 nm

    • Which of the following is NOT a characteristic of ionotropic receptors?

    <p>They require second messengers.</p> Signup and view all the answers

    Which ionotropic receptor family is noted for glutamatergic neurotransmission?

    <p>NMDA receptors</p> Signup and view all the answers

    Which ionotropic receptor is specifically associated with acetylcholine?

    <p>nACh receptor</p> Signup and view all the answers

    Which of the following neurotransmitter receptors are primarily linked to inhibition?

    <p>GABAA and Glycine Receptors</p> Signup and view all the answers

    What is the first step in the life cycle of neurotransmission?

    <p>Synthesis</p> Signup and view all the answers

    Which receptors are involved in the excitatory neurotransmission?

    <p>AMPA/Kainate and NMDA Receptors</p> Signup and view all the answers

    What is the primary function of neurotransmitter inactivation?

    <p>To terminate the action of neurotransmitters</p> Signup and view all the answers

    What is the composition of NMDAR?

    <p>Two GluN1 subunits and either two GluN2 or a combination of GluN2 and GluN3 subunits</p> Signup and view all the answers

    Which subunit is essential for forming a functional pore in NMDAR?

    <p>GluN1</p> Signup and view all the answers

    Which subunit provides the glycine-binding site for the NMDA receptor?

    <p>Both GluN1 and GluN3</p> Signup and view all the answers

    What does the NMDA receptor predominantly contribute to in excitatory postsynaptic current (EPSC)?

    <p>Individual contributions of NMDA receptors</p> Signup and view all the answers

    Which type of antagonists are used to evaluate the contributions of NMDA and AMPA receptors?

    <p>Pharmacological antagonists</p> Signup and view all the answers

    What role do GluN2 subunits play in the NMDA receptor?

    <p>They contain the glutamate binding sites</p> Signup and view all the answers

    What can be inferred about NMDAR if its function is disturbed?

    <p>It may affect synaptic plasticity and learning</p> Signup and view all the answers

    What happens to the excitatory postsynaptic current when NMDA receptors are inhibited?

    <p>Only AMPA contributions are observed</p> Signup and view all the answers

    What role do the negatively charged amino acids in the M2 segment play?

    <p>They provide cation selectivity.</p> Signup and view all the answers

    What is the format of neuronal nicotinic ACh receptors?

    <p>Composed of five identical subunits.</p> Signup and view all the answers

    How does ACh access its binding sites?

    <p>By entering through channels that provide access to the binding sites.</p> Signup and view all the answers

    What happens when the binding sites of the receptor are occupied?

    <p>The receptor rapidly opens to allow ion flow.</p> Signup and view all the answers

    What structural change occurs in the receptor during the closed-to-open transition?

    <p>There is a subtle rotation of the M2 segments.</p> Signup and view all the answers

    How many molecules of ACh does each subunit of the receptor bind?

    <p>One molecule.</p> Signup and view all the answers

    What is located at the interface between neighboring subunits of the receptor?

    <p>The ACh binding site.</p> Signup and view all the answers

    What is a characteristic of the central pore in the ACh receptor?

    <p>It provides access to the binding sites.</p> Signup and view all the answers

    What is the primary role of PSD-95 in relation to AMPARs?

    <p>Binds and localizes AMPARs at postsynaptic sites</p> Signup and view all the answers

    How does Stargazin affect the amount of AMPARs at the membrane?

    <p>Guides AMPARs to the membrane and increases their presence</p> Signup and view all the answers

    What happens in stg mice that lack Stargazin?

    <p>They lack functional AMPARs in the cerebellum despite normal GluA expression</p> Signup and view all the answers

    What is one consequence of increasing the expression of PSD-95?

    <p>Increases the anchoring of AMPARs to the synapse</p> Signup and view all the answers

    What effect does increasing Stargazin expression have on the evoked response to glutamate?

    <p>Has no effect on the evoked response</p> Signup and view all the answers

    Which of the following describes the relationship between Stargazin and PSD-95?

    <p>Stargazin guides AMPARs to the membrane and anchors them via PSD-95</p> Signup and view all the answers

    What is the consequence of TARPs composition differing across the brain?

    <p>It results in different regulatory effects on AMPAR trafficking</p> Signup and view all the answers

    How does Stargazin influence the AMPAR response to bath application of glutamate?

    <p>It increases presence of AMPARs but does not change evoked response</p> Signup and view all the answers

    In what key aspect does the trafficking of ionotropic glutamate receptors differ from mGluRs?

    <p>Ionotropic receptors are localized at the postsynaptic density</p> Signup and view all the answers

    What is the primary function of TARPs in AMPAR regulation?

    <p>To regulate trafficking, localization, and gating of AMPARs</p> Signup and view all the answers

    Study Notes

    NMDA Receptors: Structure

    • NMDA receptors are composed of two GluN1 subunits and either two GluN2 subunits or a combination of GluN2 and GluN3 subunits.
    • GluN1 is essential for the formation of a functional pore to permit the flow of ions.
    • GluN1 or GluN3 subunits provide the glycine-binding site for the receptor.
    • GluN2 subunits contain the glutamate binding sites.

    NMDA Receptors: Function

    • AMPA and NMDA receptors contribute to the total excitatory postsynaptic current (EPSC) in the brain.
    • Pharmacological antagonists can be used to dissect the individual contributions of AMPA and NMDA receptors to the EPSC.
    • NMDARs are permeable to calcium ions, which play a critical role in signal transduction and synaptic plasticity.

    NMDA Receptor Subunit Diversity

    • Subunit composition of the NMDA receptor determines its properties.

    Neurotransmitter Receptor Families

    • Neurotransmitters bind to receptors to trigger post-synaptic responses.
    • Neurotransmitter receptors are categorized into two major families: ionotropic and metabotropic receptors.
    • Ionotropic receptors are ligand-gated ion channels.
    • Metabotropic receptors are G protein-coupled receptors.

    Ionotropic Receptor Families

    • nACh receptors are a family of ionotropic acetylcholine receptors.
    • 5-HT3 receptors are a family of ionotropic serotonin receptors.
    • GABAA and Glycine Receptors are families of ionotropic receptors that are responsible for inhibitory neurotransmission in the brain.
    • Purinergic receptors are a family of ionotropic receptors that are activated by ATP.
    • Glutamatergic ionotropic receptors are a family of ionotropic receptors that are activated by glutamate, a major excitatory neurotransmitter in the brain.
    • AMPA/Kainate receptors are ionotropic glutamate receptors associated with rapid excitatory signaling.
    • NMDA receptors are ionotropic glutamate receptors that are essential for synaptic plasticity, learning and memory.

    nACh Receptor: an Iconic Ionotropic Receptor

    • Some neuronal nicotinic acetylcholine receptors (nAChRs) are composed of five identical subunits.
    • These receptors are thought to bind five molecules of acetylcholine.
    • Each subunit binds one molecule of acetylcholine at the acetylcholine binding site.
    • The acetylcholine binding site is located at the interface between neighboring subunits.
    • The acetylcholine binding site is located in the central pore of the receptor.
    • Each subunit binds one molecule of acetylcholine at the acetylcholine binding site, which is located at the interface between neighboring subunits.
    • When acetylcholine binds to the receptor, the receptor rapidly opens to allow ion flow.

    Distribution of Ionotropic Glutamate Receptors: Postsynaptic Density (PSD)

    • The postsynaptic density is the region of the postsynaptic membrane that is directly opposite the presynaptic terminal.
    • The PSD contains a high concentration of proteins, including ionotropic glutamate receptors, scaffolding proteins and signaling molecules.
    • PSD-95 is a scaffolding protein that binds to NMDA receptors, AMPA receptors and other proteins.
    • PSD-95 localizes and concentrates NMDA and AMPA receptors at postsynaptic sites.
    • Transmembrane AMPA receptor regulatory proteins (TARPs) strongly regulate the trafficking, synaptic localization, and gating of AMPARs.
    • Stargazin is an example of a TARP.

    AMPAR Trafficking is Complex and Tightly Controlled

    • AMPAR trafficking is regulated by multiple factors, including phosphorylation, ubiquitination, and interactions with other proteins.
    • The composition of TARPs can vary across different brain regions.

    TARPs: Stargazin

    • The stargazin protein plays a critical role in the trafficking and synaptic localization of AMPA receptors.
    • Knockout mice lacking Stargazin (stg mice) show a lack of functional AMPARs in the cerebellum despite normal expression of GluA subunits.
    • Increasing the expression of Stargazin increases the presence of AMPARs in the membrane.
    • Increasing the expression of PSD-95 increases the presence of AMPARs in the synapse.
    • Stargazin guides AMPARs to the membrane and anchors them to the synapse.
    • Stargazin interacts with PSD-95 via its PDZ domain.

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    Description

    This quiz covers the structural composition and functional roles of NMDA receptors in the brain. It highlights the significance of various subunits and their contributions to excitatory synaptic currents. Test your understanding of NMDA receptors and their implications in neuroscience.

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