Neurotransmitter Receptors I: Ionotropic Receptors
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Questions and Answers

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

  • Storage
  • Transmitter Inactivation
  • Receptor Binding
  • Synthesis (correct)

    • Which of the following ionotropic receptor families is NOT mentioned in the outline?

  • GABA B receptor (correct)
  • Purinergic Receptors
  • nACh receptor
  • 5-HT3 Receptor

    • Which receptors are classified as glutamatergic ionotropic receptors?

  • AMPA/Kainate and NMDA receptors (correct)
  • 5-HT3 and Glycine receptors
  • nACh and GABAA receptors
  • Purinergic and GABAB receptors

    • During which stage of neurotransmission do neurotransmitters act on their respective receptors?

    <p>Receptor Binding</p> Signup and view all the answers

    What role is indicated by transmitter inactivation in the life cycle of neurotransmission?

    <p>Preventing excessive stimulation</p> Signup and view all the answers

    What structural feature of the M2 segment contributes to cation selectivity?

    <p>Three rings of negatively charged amino acids toward the central pore</p> Signup and view all the answers

    How many molecules of ACh can each subunit of the nACh receptor bind?

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

    Where are the ACh binding sites located in the nACh receptor?

    <p>At the interface between neighboring subunits</p> Signup and view all the answers

    What occurs when the ACh binding sites are occupied?

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

    What indicates the transition from a closed to an open state in the nACh receptor?

    <p>A subtle rotation of its M2 segments</p> Signup and view all the answers

    What is the composition of some neuronal nicotinic ACh receptors?

    <p>Five identical subunits</p> Signup and view all the answers

    How does ACh gain access to its binding sites?

    <p>By entering the central pore of the receptor</p> Signup and view all the answers

    What type of receptor is the nACh receptor classified as?

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

    What is the primary function of GluN1 subunits in the NMDAR structure?

    <p>They facilitate ion flow through the receptor pore.</p> Signup and view all the answers

    Which statement about NMDAR subunit composition is true?

    <p>NMDARs can include a mix of GluN2 and GluN3 subunits.</p> Signup and view all the answers

    How can the contributions of NMDA and AMPA receptors to EPSC be differentiated?

    <p>By applying pharmacological antagonists during voltage-clamp.</p> Signup and view all the answers

    What role do GluN2 subunits play within the NMDAR?

    <p>They are responsible for the glutamate binding sites.</p> Signup and view all the answers

    What is a potential consequence of disrupted NMDAR function?

    <p>Reduced synaptic transmission efficacy.</p> Signup and view all the answers

    What occurs in the presence of APV during an experiment to isolate NMDAR contributions?

    <p>The current remaining represents AMPAR contributions.</p> Signup and view all the answers

    Which subunits directly provide the glycine-binding site in NMDARs?

    <p>A combination of GluN1 or GluN3 subunits.</p> Signup and view all the answers

    What specific aspect of NMDA receptor functionality can be assessed through examining subunit diversity?

    <p>The receptor properties and functionality.</p> Signup and view all the answers

    Which amino acid in GluA2 contributes to its low permeability to Ca2+?

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

    What impact does RNA editing have on GluA2's Ca2+ permeability?

    <p>Decreases permeability</p> Signup and view all the answers

    What happens to GluA2 mRNA when the editing site complementary sequence (ECS) is deleted?

    <p>Increases unedited GluA2 mRNA to approximately 25%</p> Signup and view all the answers

    What is the consequence of prolonged exposure to glutamate on AMPA receptors?

    <p>Causes closure of the channel</p> Signup and view all the answers

    What is the likely effect of strong electrostatic repulsion in AMPA receptors?

    <p>Reduced calcium permeability</p> Signup and view all the answers

    What kind of receptor is affected by RNA editing at the Q/R site?

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

    Which process is disrupted when the editing site complementary sequence is impaired?

    <p>GluA2 RNA editing</p> Signup and view all the answers

    What does the editing of the GluA2 amino acid primarily affect?

    <p>The Ca2+ permeability of AMPA receptor channels</p> Signup and view all the answers

    Which of the following receptor types is characterized by being ionotropic and includes NMDA and non-NMDA subclasses?

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

    What mechanism causes ATP binding to influence the structure of purinergic receptors?

    <p>Iris-like expansion of the pore region</p> Signup and view all the answers

    How many subunits come together to form the native receptor structure in purinergic receptors?

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

    Which pharmacological agents are mentioned as NMDA receptor antagonists?

    <p>CNQX and APV</p> Signup and view all the answers

    In regards to glutamate receptors, what distinguishes the AMPA receptor from NMDA receptors?

    <p>Calcium permeability</p> Signup and view all the answers

    What is the role of the M2 loop in AMPA receptors?

    <p>Dips into and out of the cytoplasmic side</p> Signup and view all the answers

    Which characteristic of ionotropic receptors distinguishes them from metabotropic receptors?

    <p>Directly mediating ion flow</p> Signup and view all the answers

    Which cation is NOT permeable through purinergic receptors?

    <p>Mg2+</p> Signup and view all the answers

    How many transmembrane domains does each subunit of a purinergic receptor contribute?

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

    Which receptor's agonists are under investigation for pharmacological distinction between subtypes?

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

    What can the binding of glutamate to AMPA receptors result in?

    <p>Opening of ion channels for cation permeation</p> Signup and view all the answers

    What aspect of AMPA/Kainate receptors is essential for their assembly?

    <p>Receptor trafficking processes</p> Signup and view all the answers

    What effect does phosphorylation have on the nACh receptor?

    <p>Limits ion flux through transitions into a closed state</p> Signup and view all the answers

    Which subunits are phosphorylated by PKA in the nACh receptor?

    <p>γ and δ subunits</p> Signup and view all the answers

    How are functional neuronal nACh receptors generally assembled?

    <p>From multiple types of α and β subunits</p> Signup and view all the answers

    Which ion is specifically excluded from permeation through the 5-HT3 receptor?

    <p>Ca2+</p> Signup and view all the answers

    What is a common structural feature of GABAA receptors?

    <p>Two α, two β, and one γ or δ subunit</p> Signup and view all the answers

    What is the primary role of antagonists for the 5-HT3 receptor?

    <p>To treat vomiting and anxiety</p> Signup and view all the answers

    Which factor contributes to the tight ring blocking ion flow in the nACh receptor?

    <p>Mild kink in the M2 segments</p> Signup and view all the answers

    What defines the desensitization rate of different nACh receptor types?

    <p>The types of α and β subunits involved</p> Signup and view all the answers

    Which kinases phosphorylate the β subunit of the nACh receptor?

    <p>Only an unidentified tyrosine kinase</p> Signup and view all the answers

    What structural feature is unique to neuronal nAChRs like α7 subtypes?

    <p>Able to be assembled from a single subunit</p> Signup and view all the answers

    What primarily causes the flow of ions through the nACh receptor when bound with ACh?

    <p>Conformational changes in the receptor structure</p> Signup and view all the answers

    What type of receptor family does the GABAA receptor belong to?

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

    Which component is not included in the phosphorylation process of the nACh receptor?

    <p>M1 segment</p> Signup and view all the answers

    What characterizes the assembly of distinct nACh receptor types?

    <p>Flexibility in subunit combinations resulting in distinct functionalities</p> Signup and view all the answers

    Study Notes

    Neurotransmitter Receptors I: Ionotropic Receptors

    • Ionotropic receptors are a type of neurotransmitter receptor
    • These receptors directly gate ion channels
    • Neurotransmission involves a cycle of events
    • Synthesis, Storage, Release, Receptor Binding, and Transmission inactivation are key stages

    The Life Cycle of Neurotransmission

    • I. Synthesis (1-2): Neurotransmitters are produced
    • II. Storage (3): Neurotransmitters are stored in vesicles
    • III. Release (Lecture 4): Neurotransmitters are released into the synaptic cleft
    • IV. Receptor Binding (4-5): Neurotransmitters bind to receptors on the postsynaptic membrane.
    • V. Transmitter Inactivation (6-9): Neurotransmitters are removed from the synaptic cleft

    Lecture Outline

    • Overview of ionotropic receptor families
    • nACh receptor, 5-HT3 receptor, GABA-A and Glycine Receptors, Purinergic Receptors, Glutamatergic Ionotropic Receptors, AMPA/Kainate, NMDA, Receptor Localization
    • Outcome of neurotransmitter release: Type of response - postsynaptic receptor, Magnitude of response - receptor number, "state" of the receptors, and amount of neurotransmitter released

    Lonotropic and Metabotropic Receptors

    • Direct gating vs indirect gating
    • Fast actions last only milliseconds, while slower actions last seconds to minutes

    nACh Receptor: an Iconic lonotropic Receptor

    • Receptor made up of subunits
    • Two extracellular binding sites for Ach
    • Plant alkaloid nicotine activates the receptor
    • Ion flow occurs through the channel

    nACh Receptor: an Iconic lonotropic Receptor

    • Each subunit provides a component to form an ion channel
    • Hydrophobic regions (M1-M4) form α-helices spanning the membrane.
    • Negatively charged amino acids contribute to cation selectivity in the channel pore.

    5-HT3 Receptor

    • Homomeric complex (five copies of the same subunit)
    • Permeable to Na+ and K+, but not Ca2+
    • Located on peripheral primary sensory nerve endings and the mammalian CNS

    GABA, and Glycine Receptors

    • GABA receptors are typically composed of two α, two β, and one γ or δ subunit.
    • GABA binding activates the channel, allowing chloride ion influx.
    • Glycine receptors are composed of three α and two β subunits, and require multiple glycine molecules for activation.

    GABA Receptors and Disease

    • Repetitive seizures result from a decrease in GABAAR β3 subunit phosphorylation by PKC.
    • This leads to increased internalization of synaptic GABA receptors.
    • This causes a reduced inhibitory effect.

    Purinergic Receptors

    • lonotropic receptors for ATP (adenosine triphosphate)
    • ATP serves as an excitatory transmitter.

    Glutamate Receptors

    • Development of agonists that can pharmacologically distinguish between different glutamate receptor subtypes
    • N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), Kainate

    AMPA Receptors

    • Receptor assembly and trafficking
    • Three transmembrane α-helices (M1, M3, and M4) and a loop (M2)
    • The M2 loop forms the selectivity filter in the channel
    • Glutamate binding activates the channel, enabling sodium and potassium ion flow
    • RNA editing of GluA2 can alter the calcium permeability of the channel

    NMDA Receptors

    • Critical role in development, learning, and memory, and brain injury
    • Permeable to calcium, glycine, and voltage-dependent
    • Important in controlling neuronal excitability
    • Membrane depolarization expels Mg²⁺ to allow ion flow.

    TARPs: Stargazin

    • Stargazin increases AMPAR expression at the synapse by increasing the number of AMPA receptors in the membrane.
    • Stargazin modulates AMPA receptor trafficking, affecting their localization and function.
    • Affects glutamate receptor function and synaptic plasticity.

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    Neurotransmitter Receptors I: Ionotropic Receptors PDF

    Description

    This quiz covers the key concepts of ionotropic receptors, a type of neurotransmitter receptor that directly gates ion channels. It includes an overview of the neurotransmission life cycle, including synthesis, storage, release, receptor binding, and inactivation. Learn about specific ionotropic receptor families such as nACh, GABA-A, and NMDA receptors.

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