Neurophysiology Voltage Clamp Quiz
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Questions and Answers

What term describes the difference between membrane potential and equilibrium potential?

  • Electrochemical gradient (correct)
  • Voltage clamp
  • Unitary current
  • Current value

    • What happens to the current Iq at the reversal potential?

  • It fluctuates unpredictably
  • It increases indefinitely
  • It becomes null (correct)
  • It decreases exponentially

    • Which ion movement contributes to the formation of inward current?

  • Flow of positive ions into the cell (correct)
  • Flow of negative ions out of the cell
  • Flow of negative ions into the cell
  • Flow of positive ions out of the cell

    • What is the effect of changing the concentration of ions on Eion?

    <p>It alters the equilibrium potential</p> Signup and view all the answers

    During voltage clamp techniques, what can be measured at the holding membrane potential (Vh)?

    <p>Current flow</p> Signup and view all the answers

    At which membrane potential does the current Iq reverse according to the characterizations provided?

    <p>Around 0 mV</p> Signup and view all the answers

    What is the primary application of the voltage clamp method in neurophysiology?

    <p>To measure current flow under controlled voltage conditions</p> Signup and view all the answers

    What describes the relationship between ion concentrations and membrane potential?

    <p>Membrane potential is determined by the electrochemical gradient</p> Signup and view all the answers

    What is the primary function of synaptic cell adhesion molecules in relation to receptor stability?

    <p>They anchor and stabilize receptors in the postsynaptic membrane.</p> Signup and view all the answers

    What dictates the polarity of the current through GABAA receptors?

    <p>The concentration of intracellular Cl-</p> Signup and view all the answers

    During development, what effect does GABA have in immature neurons?

    <p>It can depolarize the neuron.</p> Signup and view all the answers

    In which mode does a patch-clamp amplifier measure the current flowing over the membrane?

    <p>Voltage-clamp mode only.</p> Signup and view all the answers

    What causes the increase in EGABA during development?

    <p>Increase in intracellular Cl-</p> Signup and view all the answers

    What does the I/V curve represent in electrophysiological studies?

    <p>The relationship between current and voltage.</p> Signup and view all the answers

    What chloride transporter has early expression in immature neurons?

    <p>NKCC1</p> Signup and view all the answers

    What indicates a positive current value in electrophysiological measurements?

    <p>Outward current by convention.</p> Signup and view all the answers

    Which of the following is most likely to affect AMPA receptor (AMPA-R) mediated excitatory postsynaptic potentials?

    <p>Changing the extracellular solution's ion concentration.</p> Signup and view all the answers

    In mature neurons, which chloride exporter has a delayed expression?

    <p>KCC2</p> Signup and view all the answers

    What is a potential result of GABA signaling in immature neurons?

    <p>GABA can induce action potentials.</p> Signup and view all the answers

    How does Current-clamp mode differ from Voltage-clamp mode in terms of measurement focus?

    <p>It measures the membrane voltage continuously.</p> Signup and view all the answers

    What is the significance of the chloride driving force in immature neurons?

    <p>It can be reversed due to increased intracellular Cl-.</p> Signup and view all the answers

    What is the significance of holding voltage Vh in experiments measuring AMPA-R?

    <p>It sets the baseline for current flow measurement.</p> Signup and view all the answers

    Which of the following best describes GABA's role in immature neurons compared to mature neurons?

    <p>GABA transitions from excitatory to inhibitory during development.</p> Signup and view all the answers

    Which method is primarily used to measure AMPA-R mediated excitatory postsynaptic currents?

    <p>Whole Cell patch-clamp.</p> Signup and view all the answers

    What role does Ca2+ excitotoxicity play in ALS?

    <p>It is a probable cause of motorneuron cell death.</p> Signup and view all the answers

    At which membrane potential (Vm) is Eion positioned in the GABAA-R mediated ion flux graph?

    <p>-60 mV</p> Signup and view all the answers

    What role do synaptic cell adhesion molecules (SAMs) play in synapse development?

    <p>They drive synapse maturation and control synaptic properties.</p> Signup and view all the answers

    What does the GABAA receptor specifically allow to permeate?

    <p>Cl- ions</p> Signup and view all the answers

    Which variable represents the ion concentration on the outside of the cell in the Nernst Equation?

    <p>ion e</p> Signup and view all the answers

    Which neurotransmitter receptors are anchored at the postsynaptic density by MAGUKs?

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

    In the context of GABAA receptor function, what does an increase in Vm indicate?

    <p>A decrease in synaptic inhibition.</p> Signup and view all the answers

    In neurodevelopmental disorders, which of the following is NOT listed as implicated?

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

    How does the Nernst Equation relate to the potential across a membrane?

    <p>It calculates the reversal potential for a specific ion.</p> Signup and view all the answers

    What is the significance of the postsynaptic density (PSD)?

    <p>It anchors postsynaptic receptors and is critical for synaptic signaling.</p> Signup and view all the answers

    Which of the following best describes how SAMs affect synapses?

    <p>SAMs contribute to both the making and shaping of synapses.</p> Signup and view all the answers

    What is the effect of inhibitory postsynaptic potentials mediated by GABAA receptors on motorneuron activity?

    <p>They suppress motorneuron firing.</p> Signup and view all the answers

    What is the primary permeability characteristic of GABAA receptors?

    <p>They are mainly permeable to Cl-.</p> Signup and view all the answers

    What is the primary action of the GABAA receptor in adult neurons?

    <p>It causes an outward current that hyperpolarizes the membrane.</p> Signup and view all the answers

    How does the chloride concentration differ between adult and young neurons in relation to GABA?

    <p>Young neurons have a higher chloride concentration than adult neurons.</p> Signup and view all the answers

    What is one unique feature of NMDA receptors compared to other glutamate receptors?

    <p>They are subject to a voltage-dependent block by Mg2+.</p> Signup and view all the answers

    What role do MAGUKs play in the postsynaptic scaffold?

    <p>They interact with ionotropic glutamate receptors.</p> Signup and view all the answers

    Which of the following best describes the kinetics of NMDA receptors?

    <p>They exhibit slow kinetics due to slow glutamate unbinding.</p> Signup and view all the answers

    What physiological effect is attributed to the high permeability of NMDA channels to Ca2+?

    <p>It plays a role in long-term synaptic plasticity.</p> Signup and view all the answers

    What is primarily located at the tip of the dendritic spine?

    <p>Postsynaptic scaffold.</p> Signup and view all the answers

    What is the function of PDZ domains in MAGUK proteins?

    <p>They mediate protein-protein interactions.</p> Signup and view all the answers

    Study Notes

    Molecular Neurophysiology: From Molecules to Systems

    • The presentation is about molecular neurophysiology, focusing on the transition from molecules to systems.
    • The speaker, Jochen Winterer, is from the Lab of Systems Neuroscience and the Institute for Neuroscience at ETH Zurich.
    • The presentation includes diagrams and figures illustrating synaptic complexes, pre- and postsynaptic elements, and a canonical design of a central synapse.
    • The lecture highlights the interplay between electrical and chemical signaling at the synapse.

    Synaptic Complex

    • The previous lecture covered electrical signaling, transforming it into a chemical signal at the presynaptic terminal.
    • This lecture focuses on the postsynaptic side of the synapse, demonstrating how the chemical signal is translated back into an electrical signal.

    Postsynaptic and Transsynaptic Signaling

    • This section introduces the concept of postsynaptic and transsynaptic signaling in neurophysiology.
    • It emphasizes the importance of the postsynaptic receptors and synaptic cell adhesion molecules.

    Canonical Design of a Central Synapse

    • The canonical design of a central synapse is discussed, featuring postsynaptic receptors, scaffold (postsynaptic density), and synaptic cell adhesion molecules.
    • Components of the presynaptic terminal and postsynaptic cell are highlighted.
    • Vesicles, active zones, and other specialized areas are identified.

    Postsynaptic Receptors of Neurotransmitters

    • Glutamate and GABA are the most prevalent excitatory and inhibitory neurotransmitters in mammalian brains, respectively.
    • Postsynaptic receptors for glutamate include ionotropic receptors (AMPAR, NMDAR, Kainate-Rs) and metabotropic receptors (mGluRs).
    • Postsynaptic receptors for GABA include ionotropic (GABAA-Rs, GABAB-Rs) and metabotropic receptors.

    Glutamatergic and GABAergic Synaptic Transmission

    • Glutamatergic transmission leads to depolarization.
    • GABAergic transmission leads to hyperpolarization.
    • Examples of signals (EPSPs and IPSPs) and their effects are shown graphically.

    Synaptic Transmission

    • Synapses act as fundamental computational units within neuronal circuits.
    • Precise interactions between pre- and postsynaptic neurons shape synaptic properties by using different neurotransmitters and their receptors for the excitation/inhibition.
    • Postsynaptic receptor properties dictate the outcomes of activation, by defining which ion fluxes cause depolarization or hyperpolarization.

    How to Depolarize/Hyperpolarize a Cell

    • Depolarization and hyperpolarization are caused by influx or efflux of ions (cations/anions).
    • These processes are not always obvious because of the complexities of the membrane transport mechanisms.

    Questions/Learning Objectives

    • The presentation outlines questions about the properties of postsynaptic receptors, their anchoring mechanisms, and the role of synaptic adhesion molecules.
    • Receptor measurement methods are discussed as learning objectives to characterize their properties.

    How to Measure AMPA-R Mediated Excitatory Postsynaptic Potentials/Signals

    • Whole-cell patch-clamp allows measuring membrane voltage.
    • Current-clamp mode follows the voltage change in the cell membrane.
    • Voltage-clamp mode measures current to control the voltage.

    Characterizing AMPA-R

    • Characterization methods are described, including using quisqualate and recording outward/inward currents.
    • How to interpret the results are discussed

    I/V Curve

    • The relationship between current (I) and voltage (V) is described by the I/V curve.
    • Current flow (outward or inward) depends on the voltage where it is measured.

    Quick Recap: Ion Concentrations and Membrane Potential

    • The presentation reminds students about ion concentrations (intracellular and extracellular) and their gradients, as well as their significance in generating the membrane potential.
    • Concentration and electrical gradients are essential in ion transportation/movement

    Quick Recap: Ion Concentrations and Membrane Potential

    • Equilibrium potential (Eion) is described with reference to the Nernst equation in combination with membrane potentials.
    • Membrane potential differences are compared to equilibrium potentials to determine the direction of the ion flux.

    Characterization of the AMPA Receptor

    • The method for obtaining unitary currents as a function of holding membrane potential was discussed.

    • The presentation explains how to derive and use the equilibrium potential to determine the permeabilities of the ion channels.

    Characterization of the AMPA-R

    • The effect of changing external Na+ concentration on reversal potential helps identify Na+ permeability.

    Summary

    • The AMPA receptor permits the passage of Na+ and K+ ions.

    Structure and Subunit Composition of AMPA-R

    • AMPA receptors are tetramers composed of GluA1, GluA2, GluA3, and GluA4 subunits.
    • Different subunit combinations lead to functional distinctions, important in neuronal physiology

    AMPA-R Editing

    • Editing of GluA2, a process occurring at the M2 transmembrane domain, is described.
    • The conversion of glutamine to arginine at codon 586 leads to different Ca2+ permeabilities.

    Channel Conductance of GluA2 Containing vs. Lacking AMPA Receptors

    • Differences in channel conductance between GluA2-containing and GluA2-lacking AMPA receptors.

    GluA2-Editing in Amyotrophic Lateral Sclerosis (ALS)

    • Reduced ADAR2 expression in sporadic ALS may affect GluA2 editing leading to Ca2+ permeability and excitotoxicity.
    • Ca2+ excitotoxicity is a crucial mechanism contributing to neuronal death in ALS.

    Summary

    • The summarized information regarding the differences between AMPA receptor subtypes, particularly GluA2-containing and GluA2-lacking receptors.

    GABAA-R Mediated Inhibitory Postsynaptic Potential/Current

    • Transmission using GABA and its influence on postsynaptic potentials, and how it can be measured.

    Characterizing GABAA-R Mediated Ion Flux

    • The permeable ions across the GABAA receptor are identified, specifically, Cl-.

    Intracellular Cl- Concentration Dictates Polarity of Current through GABAA Receptors

    • Intracellular Cl- concentration significantly impacts the polarity of current through GABAA receptors.
    • GABA can be depolarizing.

    GABA is Depolarizing During Development

    • GABA's role and impact during brain development, where it might be depolarizing rather than inhibitory in immature neurons.

    EGABA During Development

    • The change in GABA equilibrium potential (EGABA) during development is correlated to the change of intracellular chloride concentration (and the timing of expression of ion transporters).

    Summary

    • The summarized information regarding the different effects, inhibitory and excitatory, that GABA can have based on its influence on intracellular chloride concentration.

    The NMDA Receptor

    • NMDA receptor-mediated EPSPs are broader than other EPSPs.

    Characterization of the NMDA Receptor

    • The presentation details how the method to study the NMDA receptor, in particular how to obtain the I/V curve and the involvement of Mg2+ ions.

    Effect of Physiological [Mg2+]out on the NMDA-R

    • NMDA receptors exhibit voltage-dependent Mg2+ block.
    • The influx of Mg2+ alters the shape of the I/V curve.

    The NMDA Channel is Highly Permeable to Monovalent Cations and to Ca2+

    • The NMDA receptor exhibits high permeability to monovalent cations and Ca2+.
    • The concentration of extracellular Ca2+ affects the receptor's current responses.

    Summary

    • The different qualities unique to NMDA receptors.

    Definition of Anatomical and Functional Parts of a Synapse

    • Parts of the synapse and their function.

    Postsynaptic Scaffold

    • The scaffold (postsynaptic density, PSD), including anchoring of postsynaptic neurotransmitter receptors and their interactions using proteins like MAGUKs (especially PSD95) and their PDZ domains.

    MAGUKs are Essential for Anchoring AMPA and NMDA Receptor Complexes at the Postsynaptic Density

    • Evidence that MAGUKs are crucial for the anchoring of the AMPA and NMDA receptors on the postsynaptic density, and experimental approaches that demonstrate this.

    Transsynaptic Signaling

    • SAMs are described as synaptic organizers, including their pre- and postsynaptic signaling pathways

    SAMs, the "making" and "shaping" of synapses

    • The role of synaptic cell adhesion molecules (SAMs) in synapse formation and maturation is described.
    • Data shows how changes in these SAMs impact synapse properties.

    Cell-Adhesion Molecules and the Postsynaptic Density Protein Shank in Neurodevelopmental Disorders

    • Overview of cell adhesion molecules (CAMs) and their involvement in neurodevelopmental disorders.
    • The role of SHANK, a postsynaptic density protein, in ASD, schizophrenia, epilepsy, and intellectual disabilities.

    Summary

    • PSD, its function in holding neurotransmitter receptors.
    • SAMs, their function in synaptic signaling and regulation.

    Summary

    • The overview of findings regarding the postsynaptic density (PSD) and SAMs (synaptic adhesion molecules) emphasizing their function in the brain and implications in disorders.

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    Molecular Neurophysiology PDF

    Description

    Test your understanding of voltage clamp techniques and their applications in neurophysiology. This quiz covers key concepts such as membrane potential, ion movement, and the effects of various ions on current reversal. Perfect for students and enthusiasts looking to deepen their knowledge in this area.

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