Electrophysiology Chapter on Membrane Potentials
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Questions and Answers

What triggers the opening of ligand-gated ion channels?

  • A change in membrane potential
  • Increase in intracellular calcium concentration
  • Mechanical stretch causing a conformational change
  • The binding of a neurotransmitter to a receptor (correct)
  • Which ion movement is primarily responsible for the hyperpolarized state of the cell at rest?

  • High intracellular sodium ion concentration
  • High extracellular sodium ion concentration
  • High extracellular potassium ion concentration
  • High intracellular potassium ion concentration (correct)
  • What role does the sodium/potassium pump play in generating the resting membrane potential?

  • It maintains the concentration gradient by moving Na+ out and K+ in. (correct)
  • It increases chloride ion concentration inside the cell.
  • It creates a rapid depolarization of the membrane.
  • It directly contributes most of the -75 mV membrane potential.
  • Which cellular event occurs when the cell membrane potential becomes more positive?

    <p>The cell becomes depolarized. (B)</p> Signup and view all the answers

    Which mechanism opens voltage-gated ion channels?

    <p>Alteration in membrane potential (D)</p> Signup and view all the answers

    What is the typical polarity of the resting membrane potential in a cell, and what does this indicate about the intracellular environment relative to the extracellular environment?

    <p>Negative, indicating a lower concentration of positive ions intracellularly. (A)</p> Signup and view all the answers

    Which of the following accurately distinguishes between graded potentials and action potentials?

    <p>Graded potentials are typically initiated by synaptic input or sensory stimuli, while action potentials are triggered by reaching a threshold. (B)</p> Signup and view all the answers

    What is the primary distinction between intracellular recording (current clamp) and patch clamp recording techniques in electrophysiology?

    <p>Intracellular recording typically measures the membrane potential of a whole cell, while patch clamp allows for the study of current flow through single or multiple ion channels. (C)</p> Signup and view all the answers

    According to standard electrophysiological conventions, which of the following voltage deflections would be represented as an 'upwards' trace on a recording?

    <p>Depolarization, indicating an increase in membrane potential. (B)</p> Signup and view all the answers

    In electrophysiological current recordings, what does a 'downwards' trace typically indicate?

    <p>Inward positive current, moving positive ions into the cell. (C)</p> Signup and view all the answers

    During intracellular recording, injecting a negative current into a neuron would typically result in:

    <p>Hyperpolarization of the membrane, making the membrane potential more negative. (C)</p> Signup and view all the answers

    What is the significance of the 'threshold level of depolarization' in the context of action potentials?

    <p>It is the minimum level of depolarization required to trigger the opening of voltage-gated ion channels and initiate an action potential. (A)</p> Signup and view all the answers

    What is the fundamental basis for the resting membrane potential (RP) in cells?

    <p>Selective permeability of the cell membrane to different ions and the electrochemical gradients across the membrane. (D)</p> Signup and view all the answers

    What is the effect of hyperpolarization on potassium ion efflux?

    <p>Potassium ion efflux is low and steady. (D)</p> Signup and view all the answers

    What does the equation $VM = \sum {P_{ION} \times E_{ION}}$ represent?

    <p>The membrane potential considering ionic permeability and equilibrium potentials. (A)</p> Signup and view all the answers

    Which method determined the structure of eukaryotic ion channels?

    <p>Cryo-electron microscopy (D)</p> Signup and view all the answers

    In the context of ionic channels, what can be inferred by the hydrophobicity plot of a gene sequence?

    <p>The association of subunits with the cell membrane (D)</p> Signup and view all the answers

    What is the role of the selectivity filter in the KcsA channel?

    <p>To determine which ions pass through the channel (C)</p> Signup and view all the answers

    In a depolarized state near ENa+, what is the noted driving force for sodium ions (Na+)?

    <p>Very low (D)</p> Signup and view all the answers

    What distinguishes the KcsA bacterial K+ channel in structural studies?

    <p>Its structure was determined using X-ray crystallography. (C)</p> Signup and view all the answers

    What does the Nernst equation calculate in the context of cellular membranes?

    <p>Equilibrium potential of a specific ion (A)</p> Signup and view all the answers

    In the equivalent circuit model of a nerve cell membrane, what does RM represent?

    <p>Trans-membrane input resistance (C)</p> Signup and view all the answers

    Which aspect is crucial for the study of ion channels using the patch clamp method?

    <p>Measuring ionic currents individually (D)</p> Signup and view all the answers

    Which ion has the highest permeability at rest in a nerve cell?

    <p>Potassium (K+) (B)</p> Signup and view all the answers

    How does myelin influence the trans-membrane input resistance (RM) and membrane capacitance (CM)?

    <p>Increases RM and decreases CM (D)</p> Signup and view all the answers

    What component of the nerve cell is modeled as a current generator in the equivalent circuit?

    <p>Na/K pump (C)</p> Signup and view all the answers

    What is the main significance of the Goldman-Hodgkin-Katz equation for membrane potential?

    <p>It sums all equilibrium potentials weighted by permeability (B)</p> Signup and view all the answers

    How does the diameter of an axon influence axoplasmic (internal) resistance (RI)?

    <p>Larger diameter decreases RI (B)</p> Signup and view all the answers

    Which factor is most crucial in determining the resting membrane potential relative to the equilibrium potential?

    <p>Potassium efflux (A)</p> Signup and view all the answers

    The Nobel Prize in Physiology or Medicine in 1991 was awarded for the discovery of which technique?

    <p>Patch clamp recording of single ion channels (C)</p> Signup and view all the answers

    For a voltage-gated $Na^+$ channel, membrane depolarization primarily induces:

    <p>Channel opening, enabling $Na^+$ influx (B)</p> Signup and view all the answers

    Ionic current measured across a cell membrane is best described as the:

    <p>Sum of ion fluxes through all open channels (A)</p> Signup and view all the answers

    The lipid bilayer of a nerve cell membrane primarily functions as a:

    <p>Barrier against ion diffusion, maintaining concentration gradients (B)</p> Signup and view all the answers

    Membrane pumps in nerve cells are essential for:

    <p>Establishing and maintaining ion concentration gradients (D)</p> Signup and view all the answers

    Ion channel selectivity refers to the:

    <p>Preference for permeation of certain ion types over others (D)</p> Signup and view all the answers

    Which of the following is NOT identified as a primary gating stimulus for ion channels in nerve cells?

    <p>Cytoskeletal rearrangement (A)</p> Signup and view all the answers

    Biochemical-gated ion channels are directly regulated by:

    <p>Intracellular signaling molecules such as G proteins or cyclic nucleotides (B)</p> Signup and view all the answers

    What role do oocytes play in studying ion channels?

    <p>They are used to express injected exogenous mRNA coding for channel proteins. (B)</p> Signup and view all the answers

    How can mutated ion channels be studied using oocytes?

    <p>By comparing their responses using patch clamp electrophysiology. (A)</p> Signup and view all the answers

    Which state transitions are exhibited by Na channels in response to membrane potential changes?

    <p>Na channels open with depolarization and inactivate subsequently. (C)</p> Signup and view all the answers

    What distinguishes the K channel studied in oocytes from those involved in resting potential?

    <p>The K channel in oocytes opens with depolarization and closes with hyperpolarization. (C)</p> Signup and view all the answers

    Which disease is associated with mutations in neuronal Na+ channels?

    <p>Generalized Epilepsy with Febrile Seizures Plus types I and II (B)</p> Signup and view all the answers

    What role does the patch clamp technique serve in studying ion channels?

    <p>It records the electrical activity of ion channels in membranes. (A)</p> Signup and view all the answers

    Which muscle-related disorder is associated with Na+ channel mutations?

    <p>Paramyotonia Congenita (A)</p> Signup and view all the answers

    How does Ohm's law relate to ion channels as electrical conductors?

    <p>Ion channel conductance can sometimes disobey Ohm’s law. (A)</p> Signup and view all the answers

    Flashcards

    Resting Membrane Potential (VM)

    The difference in electrical potential between the inside and outside of a cell membrane. At rest, the inside of the cell is typically negatively charged compared to the outside.

    Electrochemical equilibrium

    The movement of ions across the cell membrane, driven by both electrical and chemical gradients.

    Selective permeability

    The ability of a cell membrane to allow certain ions to pass through more easily than others.

    Driving Force

    The force that drives ions across the membrane, determined by the concentration gradient and the electrical potential difference.

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    Graded Potential

    A type of membrane potential change that is localized and decays with distance. It is caused by a transient influx or efflux of ions.

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    Action Potential

    A rapid, transient depolarization of the membrane potential that travels along the axon, allowing communication between neurons.

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    Intracellular Recording

    A technique used to measure the electrical activity of a cell by inserting a microelectrode into the cell's interior.

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    Patch Clamp Recording

    A technique used to measure the flow of ions across the cell membrane by recording the electrical current through a small patch of membrane.

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    Voltage-gated ion channels

    A type of protein channel that is opened or closed in response to changes in the membrane potential. These channels play a critical role in generating and propagating action potentials.

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    Ionic current

    The movement of ions across a cell membrane through a channel, driven by the concentration gradient and the electrical potential difference.

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    Ion channel selectivity

    The selective permeability of an ion channel to specific types of ions. For example, a sodium channel allows sodium ions to pass through but not potassium ions.

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    Ligand-Gated Channel

    This type of channel opens in response to a specific neurotransmitter binding to its receptor. The binding triggers a conformational change in the receptor, which opens the channel allowing ions to flow through the membrane.

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    Voltage-Gated Channel

    This type of channel opens in response to changes in membrane potential. When the voltage across the membrane reaches a certain threshold, it causes a conformational change in the channel, allowing ions to flow through.

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    Ion channel gating

    The process by which a stimulus triggers the opening or closing of an ion channel.

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    Biochemical-gated ion channel

    A type of ion channel gated by the binding of a specific molecule, such as a neurotransmitter or a second messenger.

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    Mechanosensitive Channel

    This type of channel opens in response to mechanical force, such as stretching or pressure. The force causes a conformational change in the channel, allowing ions to flow through.

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    Membrane potential (VM)

    The electrical potential difference across the cell membrane, which is typically negative inside the cell.

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    Membrane Potential

    The potential difference across the cell membrane, resulting from the separation of charges. It is typically negative at rest, ranging from -40 mV to -100 mV.

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    Sodium-Potassium Pump

    This pump actively transports three sodium ions out of the cell and two potassium ions into the cell, resulting in a net movement of positive charge out of the cell. This contributes to the establishment of the resting membrane potential.

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    Resting potential

    The resting state of a neuron, where the membrane potential is maintained at a constant value.

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    Nernst Equation

    The Nernst equation calculates the equilibrium potential for a specific ion across a membrane, considering its concentration gradient.

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    Goldman-Hodgkin-Katz Equation

    The Goldman-Hodgkin-Katz equation calculates the membrane potential by taking into account the equilibrium potentials of all permeant ions and their respective permeabilities.

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    Resting Membrane Potential

    The resting membrane potential is the electrical potential difference across the cell membrane when the cell is in a resting state.

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    Equilibrium Potential

    The equilibrium potential is the theoretical voltage across a membrane where the electrochemical forces driving an ion across the membrane are perfectly balanced.

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    Membrane Resistance (RM)

    The membrane resistance (RM) is the resistance to the flow of charge across the cell membrane. Ion channels act as resistors, controlling the flow of ions.

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    Axoplasmic Resistance (RA)

    Axoplasmic resistance (RA) is the resistance to the flow of current within the axon. Myelin, acting as an insulator, decreases RM and increases RA.

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    Membrane Capacitance (CM)

    Membrane capacitance (CM) is the ability of the cell membrane to store electrical charge. The phospholipid bilayer acts as a capacitor.

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    Ionic driving force

    The force that drives ions across a membrane, determined by the difference between the membrane potential (VM) and the equilibrium potential (EION) for that ion.

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    Permeability (conductance)

    The permeability of the membrane to a specific ion, represented by the conductance (gION) for that ion.

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    Equilibrium potential (EION)

    The potential difference across a membrane at which there is no net movement of a specific ion.

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    Hyperpolarized membrane

    A membrane potential that is more negative than the resting membrane potential, closer to the equilibrium potential for potassium (EK+).

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    Depolarized membrane

    A membrane potential that is more positive than the resting membrane potential, closer to the equilibrium potential for sodium (ENa+).

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    Electrotonic (passive) membrane properties

    The ability of a membrane to conduct electrical signals passively, determined by the length constant and time constant.

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    Length constant

    The distance over which a signal can travel passively before decaying to 37% of its original amplitude.

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    What are oocytes used for?

    Oocytes are cells that can be used to study ion channels. They do not have their own ion channels, but they can express injected mRNA coding for channel proteins.

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    How do oocytes express ion channels?

    Oocytes can express injected exogenous mRNA coding for channel proteins and traffic these into the membrane. This allows for functional study of ion channels.

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    How are ion channels studied in oocytes?

    Patch clamp electrophysiology is a technique that allows researchers to study the function of ion channels in oocytes. They can compare normal channels to those mutated in disease.

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    What happens to sodium channels during depolarization?

    Sodium (Na+) channels are responsible for the rapid depolarization phase of action potentials. They open when the membrane potential becomes more positive and then inactivate. They close when the membrane potential returns to a negative value.

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    What happens to potassium channels during repolarization?

    Potassium (K+) channels open when the membrane potential becomes more positive and close when the membrane potential becomes more negative. They are responsible for repolarization of the action potential, but not for setting the resting membrane potential.

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    What is a channelopathy?

    Channelopathies are diseases caused by mutations in ion channel genes. These mutations can lead to problems with excitability in various tissues, including skeletal muscle and the brain.

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    What is hyperkalemic periodic paralysis?

    Hyperkalemic periodic paralysis is a channelopathy that affects skeletal muscle. It is caused by mutations in the sodium channel gene SCN4A.

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    What is generalized epilepsy with febrile seizures plus?

    Generalized epilepsy with febrile seizures plus is a channelopathy that affects the brain. It is caused by mutations in the sodium channel gene SCN1A.

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    Study Notes

    Lecture 011625

    • Bioelectric circuits and ion channels are studied using Electrophysiological Studies and Molecular Approaches.
    • Different types of channels and their gating mechanisms are explored.
    • Membrane potential concepts, including electrochemical equilibrium, resting membrane potential, selective permeability, and driving force, are explained.
    • Nernst and Goldman equations are detailed.
    • Electrotonic (passive) properties, time constants, and length constants are discussed.
    • Action potential introduction is included.

    Membrane Potentials

    • Changes in membrane potential (Vm) from resting include graded responses (synaptic potentials) and active responses (action potentials).
    • Resting membrane potential (Vm) is described as inside relative to outside, meaning cells are negatively charged at rest.

    Study of Ion Channels - Electrophysiology

    • Intracellular recording measures membrane potential by current clamp.
    • Patch clamp recording measures ionic currents, including IK+, INa+, and Ica++.
    • Recordings use conventions for voltage (depolarization as upward traces, hyperpolarization as downward traces) and current (inward current as downward traces, outward current as upward traces).
    • Membrane potential is the difference in voltage across the cell membrane.
    • Ionic current = I(ION).

    Intracellular Recording of Resting and Action Potentials

    • Injecting positive current depolarizes the membrane, while injecting negative current hyperpolarizes it.
    • A threshold level of depolarization triggers an action potential.

    Patch Clamp Recording of Single Voltage-Gated Na+ Channel

    • Membrane depolarization opens Na+ channels, leading to Na+ influx.
    • Ionic current is the sum of flux through multiple channels.

    Nerve Cell Membrane

    • The lipid bilayer acts as a barrier to ion diffusion.
    • Pumps transport ions to create concentration gradients.
    • Channels are embedded in the phospholipid bilayer, selective for ions like K+, Na+, Ca++, or Cl–, and passive (gated by varied stimuli, like change in Vm, transmitters, mechanics, or intracellular events). They regulate resting and action potentials.

    Study of Ion Channels - X-ray Crystallography

    • Crystals allow for precise distance measurements between amino acids, inferring channel structure.
    • The KcsA potassium channel's structure, including selectivity filter and pore, has been determined.
    • Bacterial and eukaryotic voltage-gated channels' structural analysis is possible.

    Study of Ion Channels - Molecular Biology

    • Gene sequences predict subunit association with the cell membrane.
    • Hydrophobicity plots of gene sequences delineate hydrophobic and hydrophilic domains.
    • Channel subunits form receptor, pore, and accessory units.
    • Examples include acetylcholine receptor (AchR) and sodium channels (NaV).

    Study of Ion Channels - Electrophysiology (Xenopus Oocyte System)

    • Xenopus oocytes are used to study ion channels because they lack native channels.
    • Exogenous mRNA for channel proteins is injected into the oocytes.
    • The oocytes traffic and insert functional channels into the membrane.
    • This technique compares normal channels to mutated “channelopathies” in disease.

    Na and K Channel Responses to VM

    • Na+ channels open during depolarization and inactivate with repolarization.
    • K+ channels open during repolarization to restore Vm to its resting potential.

    Expression of Na+ Channels in Frog Eggs

    • Na+ channels are expressed in frog egg oocytes.
    • Patch clamp is used to record the movement of ions through channels.

    Channelopathies in Skeletal Muscle and Brain

    • Various diseases (e.g., hyperkalemic periodic paralysis, hypokalemic periodic paralysis, paramyotonia congenita) are caused by abnormalities in the Na+ channels of skeletal muscles and/or the brain.

    Ion Channels as Conductors of Electricity

    • Ohmic channels follow Ohm's law (V = IR).
    • Rectifying channels are non-ohmic and their current-voltage relationship depends on the direction of the current.
    • The difference between these two is highlighted in the discussion of subthreshold responses and action potentials.

    Electrotonic (Passive) Membrane Properties

    • Time constant measures how quickly voltage changes during passive responses.
    • Length constant measures how quickly voltage changes with distance in passive responses.

    Action Potentials

    • They are used to transmit info rapidly over distances.
    • Frequency of action potentials codes the intensity of the information, with greater frequency reflecting higher intensity.
    • Recruitment of axons carrying action potential denotes information.
    • Place code distinguishes axons transmitting the action potential.
    • Voltage-gated Na+ and K+ channels are responsible for rapid, positive and negative feedback, respectively. They ensure faithful propagation of the action potential.

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    Description

    This quiz covers the fundamental concepts of bioelectric circuits and ion channels as studied through electrophysiological and molecular approaches. It explores key topics such as membrane potentials, their changes, gating mechanisms of different channels, and the application of equations like Nernst and Goldman. Additionally, the introduction to action potentials and the methods for measuring membrane potential are included.

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