Electrophysiology Quiz: Membrane Potential

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Questions and Answers

Which channel type relies on physical distortion to initiate its opening?

  • Voltage-gated
  • Mechanosensitive (correct)
  • Electrogenic pump
  • Ligand-gated

What term describes the state of a cell when its membrane potential becomes more positive than its resting membrane potential?

  • Hyperpolarized
  • Depolarized (correct)
  • Repolarized
  • Equilibrated

What is the primary direct contribution of the sodium/potassium pump to the resting membrane potential?

  • Creating a small negative membrane potential through its electrogenic nature (correct)
  • Preventing potassium ions from leaving the cell
  • Establishing high intracellular sodium concentration
  • Directly generating the majority of the resting membrane potential

Considering the distribution of ions across the cell membrane, which of the following statements is correct in a resting cell?

<p>Sodium ion concentration is higher outside the cell than inside. (A)</p> Signup and view all the answers

Which aspect of ion channel kinetics refers to the time taken for a channel to transition from a closed state to an open state upon stimulation?

<p>Opening time (D)</p> Signup and view all the answers

Which of the following best describes the state of a cell's membrane potential when it is at rest?

<p>The inside of the cell is negatively charged relative to the outside. (A)</p> Signup and view all the answers

What is the primary measurement in current clamp electrophysiology?

<p>Changes in membrane potential (C)</p> Signup and view all the answers

In electrophysiology, a 'downwards' deflection in a voltage recording trace is conventionally represented as:

<p>Hyperpolarization (B)</p> Signup and view all the answers

What is the effect on membrane potential when a positive current is injected into a cell during intracellular recording?

<p>Depolarization, making the membrane potential more positive. (C)</p> Signup and view all the answers

Which of the following is measured directly using the patch clamp technique?

<p>Ionic current (B)</p> Signup and view all the answers

In current recording conventions, an 'upwards' deflection in the trace indicates:

<p>Outward positive current (A)</p> Signup and view all the answers

What is required to reach the threshold level of depolarization in a neuron, leading to the generation of an action potential?

<p>Sufficient depolarization (C)</p> Signup and view all the answers

Which of the following changes in membrane potential is classified as an 'active response'?

<p>Action potential (A)</p> Signup and view all the answers

What is the primary value calculated by the Nernst equation in the context of neuronal membrane potential?

<p>The equilibrium potential for a specific ion based on its concentration gradient. (D)</p> Signup and view all the answers

According to the Goldman-Hodgkin-Katz (GHK) equation, what is the primary determinant of the membrane potential ($E_M$) in a cell permeable to multiple ions?

<p>The weighted sum of the equilibrium potentials of all permeable ions, considering their relative permeabilities. (B)</p> Signup and view all the answers

Which of the following factors is MOST crucial in establishing the resting membrane potential ($E_M$) in a neuron?

<p>High permeability of the membrane to potassium ions ($K^+$) through non-gated channels. (A)</p> Signup and view all the answers

At resting membrane potential, the neuronal membrane exhibits:

<p>High permeability to potassium ions ($K^+$) and low permeability to sodium ions ($Na^+$). (B)</p> Signup and view all the answers

In the equivalent circuit model of a nerve cell membrane, which component primarily represents the phospholipid bilayer's ability to store charge?

<p>Membrane Capacitance ($C_M$). (B)</p> Signup and view all the answers

Which of the following factors would primarily affect the axoplasmic resistance ($R_A$) in a neuron?

<p>The diameter of the axon. (C)</p> Signup and view all the answers

In the context of the equivalent circuit of a nerve cell membrane, ion channels are best represented as:

<p>Resistors, influencing membrane resistance ($R_M$). (D)</p> Signup and view all the answers

Myelination primarily affects which components of the equivalent circuit model of a nerve cell membrane?

<p>Membrane resistance ($R_M$) and membrane capacitance ($C_M$). (B)</p> Signup and view all the answers

For which contribution to the field of neuroscience were Sakmann and Neher awarded the Nobel Prize?

<p>Pioneering the patch clamp technique for studying single ion channel currents. (C)</p> Signup and view all the answers

What is the immediate effect of membrane depolarization on voltage-gated sodium (Na+) channels?

<p>Channel opening, causing an influx of Na+ ions. (A)</p> Signup and view all the answers

Which component of the nerve cell membrane primarily functions as a barrier to ion diffusion?

<p>The phospholipid bilayer itself. (D)</p> Signup and view all the answers

What is the principal role of ion pumps in the nerve cell membrane, in contrast to ion channels?

<p>To establish and maintain ion concentration gradients across the membrane. (B)</p> Signup and view all the answers

Ion channels exhibit selectivity, meaning they are primarily permeable to:

<p>Specific types of ions, such as K+, Na+, Ca++, or Cl-. (B)</p> Signup and view all the answers

Which of the following stimuli is LEAST likely to directly gate an ion channel, based on the provided text?

<p>Variations in ambient temperature. (B)</p> Signup and view all the answers

An 'inward current' in the context of ion channels refers to the flux of:

<p>Positive ions moving into the cell, contributing to depolarization. (C)</p> Signup and view all the answers

Biochemical-gated ion channels are characterized by their direct activation through:

<p>Intracellular signaling molecules such as G proteins, cyclic nucleotides, or Ca2+. (D)</p> Signup and view all the answers

According to Ohm's Law as applied to ionic current across a membrane, what would decrease the ionic current ($I_{ION}$)?

<p>A decrease in ionic conductance ($g_{ION}$). (A)</p> Signup and view all the answers

If a membrane is hyperpolarized to a potential close to the equilibrium potential for potassium ($E_{K+}$), what is the expected driving force for potassium ions ($K^+$)?

<p>Low driving force, resulting in minimal potassium efflux. (D)</p> Signup and view all the answers

Which of the following best describes the relationship between ionic permeability ($P_{ION}$) and ionic conductance ($g_{ION}$)?

<p>Ionic permeability is another term used to describe ionic conductance. (B)</p> Signup and view all the answers

In the equation $V_M = \sum {P_{ION} imes E_{ION}}$, what does an increase in the permeability ($P_{ION}$) of a specific ion primarily contribute to?

<p>A greater influence of the equilibrium potential ($E_{ION}$) of that specific ion on the membrane potential ($V_M$). (C)</p> Signup and view all the answers

What is the significance of 'hydrophobicity plots' in the study of ion channels?

<p>They indicate regions of a protein sequence that are likely to be located within the lipid bilayer of the cell membrane. (D)</p> Signup and view all the answers

The Nobel Prize in Chemistry was awarded for the study of ion channels using X-ray crystallography, specifically for determining the structure of which ion channel?

<p>KcsA bacterial $K^+$ channel. (D)</p> Signup and view all the answers

Which technique is described as using crystals to measure distances between amino acids to infer the structure of ion channels?

<p>X-ray crystallography. (B)</p> Signup and view all the answers

What is the purpose of using the Xenopus oocyte expression system in ion channel research?

<p>To express and study the function of ion channels by introducing foreign genetic material into Xenopus oocytes. (B)</p> Signup and view all the answers

What is a primary advantage of using oocytes in the study of ion channels?

<p>Oocytes do not express their own native ion channels, allowing researchers to study only the channels introduced via mRNA injection. (D)</p> Signup and view all the answers

Which electrophysiological technique is specifically mentioned as being used to study ion channels in oocytes?

<p>Patch clamp (A)</p> Signup and view all the answers

Following membrane depolarization (VM+), what is the typical response of a Na+ channel expressed in an oocyte?

<p>Initial inward flow of Na+ ions followed by inactivation. (D)</p> Signup and view all the answers

How does the behavior of the K+ channel described in the content differ from the K+ channel responsible for the resting membrane potential?

<p>The described K+ channel opens with depolarization (VM+), while the resting potential K+ channel is primarily involved in maintaining a stable negative membrane potential. (B)</p> Signup and view all the answers

What process allows researchers to study channelopathies using oocytes?

<p>Injecting mRNA coding for mutated ion channels into oocytes and observing their function. (B)</p> Signup and view all the answers

Which of the following is listed as a channelopathy related to brain Na+ channels?

<p>Generalized Epilepsy with Febrile Seizures Plus (D)</p> Signup and view all the answers

According to the content, how do ion channels relate to Ohm's Law?

<p>Ion channels may or may not obey Ohm's Law, suggesting their electrical conductance can be complex. (C)</p> Signup and view all the answers

What happens to the Na+ channel described in the content when the membrane potential becomes more negative (VM-), moving towards hyperpolarization?

<p>The Na+ channel closes. (C)</p> Signup and view all the answers

Flashcards

Membrane potential

The electrical difference between the inside and outside of a cell membrane.

Electrochemical equilibrium

A state where the electrical and chemical forces acting on an ion across the membrane are balanced, preventing net movement of that ion.

Resting membrane potential

The membrane potential of a cell when it is at rest, typically negative.

Selective permeability

The ability of a cell membrane to allow certain ions to pass through while restricting others.

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Driving force

The force that drives an ion across the membrane, influenced by both the concentration gradient and the electrical potential.

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Graded potential

A small, localized change in membrane potential that decays over distance and time.

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Action potential

A rapid, large change in membrane potential that travels along the axon without decreasing in amplitude.

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Intracellular recording

A technique used to study the electrical properties of cells by inserting a fine electrode into the cell's interior.

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Ligand-Gated Channels

A type of ion channel that opens or closes in response to the binding of a specific chemical messenger called a ligand.

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Voltage-Gated Channels

A type of ion channel that opens or closes in response to changes in the electrical potential across the membrane.

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Mechanosensitive Channels

A type of ion channel that opens or closes in response to mechanical forces, such as stretching or pressure.

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Ion Channels

A specialized protein embedded in the cell membrane that allows the passage of specific ions across the membrane. They are crucial for maintaining the electrical gradient and generating electrical signals in cells.

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Membrane Depolarization

The process by which the membrane potential of a neuron changes in response to a stimulus, leading to the generation of an action potential.

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Ionic Current

The flow of charged particles, specifically ions, across a cell membrane. It is the basis of electrical signaling in cells.

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Lipid Bilayer

A layer of lipids that forms a barrier between the inside and outside of a cell. It prevents the free movement of ions and other molecules across the membrane.

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Pumps

Proteins that actively transport ions across the cell membrane against their concentration gradients, using energy from ATP. They help establish and maintain the ion gradients necessary for cell function.

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Equilibrium potential

The potential difference across a membrane when an ion is in electrochemical equilibrium.

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Pion (permeability)

Describes the relative permeability of different ions across the membrane.

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Goldman-Hodgkin-Katz equation

This equation describes the relationship between membrane potential, equilibrium potentials, and permeabilities of different ions. It's similar to a weighted average: higher permeability = higher contribution.

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Transmembrane resistance (RM)

Represents the resistance to electrical current flow across the membrane.

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Axoplasmic resistance (RA)

Represents the resistance to electrical current flow along the inside of the axon.

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External resistance (RO)

Represents the resistance to electrical current flow through the external medium surrounding the axon.

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Ionic driving force

The force that drives the movement of ions across the cell membrane. Depends on both the concentration gradient and the electrical potential.

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Permeability (conductance)

The permeability of the membrane to a specific ion, determined by the number and type of ion channels present.

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Equilibrium potential (EION)

The membrane potential at which the driving force for an ion is zero, meaning no net movement of that ion across the membrane.

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Hyperpolarization

A change in membrane potential that makes the inside of the cell more negative. Decreases the driving force for potassium (K+) efflux.

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Depolarization

A change in membrane potential that makes the inside of the cell more positive, closer to the equilibrium potential for sodium (Na+). Increases the driving force for sodium influx.

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Potential change

The change in membrane potential that occurs in response to a stimulus. Can be graded or all-or-none.

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Electrotonic conduction

The spread of electrical signals passively along the membrane, without the involvement of voltage-gated ion channels.

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Why use oocytes to study ion channels?

Oocytes are unfertilized eggs that can be used to study ion channels. Oocytes normally do not have their own ion channels, so researchers can inject mRNA encoding for specific ion channels into them. These injected channels will be expressed, trafficked to the cell membrane, and become functional. This allows researchers to study the function of these channels using the patch clamp technique.

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How can mutations linked to diseases be studied in oocytes?

Oocytes are used to study the effects of mutations on ion channels by comparing the activity of normal channels with those that have mutations known to cause diseases (channelopathies) in humans. The mutations can directly affect the channel's structure, function, or regulation.

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Describe the behavior of Na+ channels during membrane depolarization.

When a cell membrane is depolarized, the voltage across the membrane becomes more positive. Na+ channels open when the membrane depolarizes, allowing Na+ ions to flow into the cell. This influx of positive charge further depolarizes the membrane, creating a positive feedback loop.

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What is inactivation of Na+ channels, and why is it important?

After being open, Na+ channels quickly inactivate. Inactivation occurs due to a conformational change in the channel protein, preventing further inflow of Na+ ions even though the membrane is still depolarized. This inactivation helps to terminate the action potential.

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What happens to K+ channels during repolarization?

K+ channels open when the membrane repolarizes (becomes more negative) after depolarization. This allows K+ ions to flow out of the cell, contributing to the repolarization process and restoring the membrane potential to its resting state.

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How do Na+ channels contribute to the generation of an action potential?

Na+ channels are voltage-gated channels, meaning they open and close in response to changes in the membrane potential. They initiate the action potential by allowing rapid influx of Na+ ions when the membrane depolarizes. This depolarization then triggers the opening of voltage-gated K+ channels, causing repolarization.

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What are channelopathies?

Channelopathies are diseases caused by mutations in ion channel genes. These mutations can affect the channel's structure, function, or regulation, leading to a wide range of symptoms, depending on the specific channel affected.

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How can expression systems be used to study channelopathies?

Expression systems, such as oocytes, allow scientists to study channelopathies by comparing the activity of mutated channels to normal channels. This allows researchers to understand how specific mutations affect channel function and to develop potential therapeutic strategies for these diseases.

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Study Notes

Lecture 011625

  • Bioelectric Circuits and Ion Channels

    • Electrophysiological Studies
    • Molecular Approach
    • Types of Channels and their Gating
  • Membrane potential

    • Electrochemical equilibrium
    • Resting membrane potential
    • Selective permeability
    • Driving Force
    • Nernst and Goldman equations
  • Electrotonic (passive) properties

    • Time and length constants - initial look
  • Action potential

    • Introduction of the concept

Membrane Potentials

  • Recording of Membrane Potential (VM)

    • Changes in VM from resting state include graded responses (synaptic potentials) and active responses (action potentials).
  • Synaptic Potential

    • A graded response; a small, temporary change in membrane potential.
  • Action Potential

    • A rapid, large change in membrane potential that is propagated along the axon.

Study of ion channels - electrophysiology

  • Intracellular recording

    • Current clamp: measures membrane potential (VM).
    • Recordings conventionally show depolarization (VM increases) as upward traces and hyperpolarization (VM decreases) as downward traces:
  • Patch clamp recording

    • Form of voltage clamp: measures ionic current.
    • Recordings conventionally show inward current (downwards trace) and outward current (upwards trace).
  • Membrane Potential = VM

  • Ionic Current = I(ION)

Intracellular recording of resting and action potentials

  • Injecting positive current: depolarization
  • Injecting negative current: hyperpolarization
  • A threshold level of depolarization can trigger an action potential.

Patch clamp recording of single voltage-gated Na+ channels

  • Stimulus: membrane depolarization
  • Effect: channel opening, Na+ influx

Nerve cell membrane

  • Lipid bilayer: barrier to ion diffusion
  • Pumps: transport ions to create concentration gradients
  • Channels: embedded in the phospholipid bilayer; selective for K+, Na+, Ca2+, or Cl-; passive flux of ions; gated by varied stimuli (e.g., changes in VM, neurotransmitters, etc.)

Study of Ion Channels - X-ray crystallography

  • KcsA bacterial K+ channel structure determined by X-ray crystallography.
  • Bacterial voltage-gated channels and eukaryotic channels have also been studied via other techniques.

Study of ion channels - Molecular Biology

  • Gene sequences predict association of subunits to cell membranes.
  • Hydrophobicity plots can be used to understand the protein's structure.

Study of ion channels - Electrophysiology

  • Xenopus oocyte expression system: oocytes are used to study ion channels because they do not express native ion channels, can express injected exogenous mRNA coding for channel proteins, and traffic and insert functional channels into the cell membrane.
  • This system useful to compare normal channel function to those mutated in disease—channelopathies.

Na and K channel responses to VM

  • Na+ channels: Na+ enters (open) then inactivates (closed) when VM changes.
  • K+ channels: K+ exits (open) when Vm changes.

Expression of Na+ channels in frog egg

  • RNA is inserted into the frog egg
  • The channels are recorded using patch clamp.

Channelopathies

  • Genetic defects in ion channels can lead to various diseases. Examples are presented for skeletal muscle Na+ channels and brain Na+ channels.

Electrotonic (passive) membrane properties

  • Time constant: time taken for the potential change to reach approximately 63% of the final value.
  • Length constant: distance over which the potential change is approximately 37% of its initial value.

Basis of Membrane Potential

  • Role of sodium/potassium pump
    • Maintains ion distribution (high Na+ outside, high K+ inside)
    • Creates a charge difference across the membrane
    • Is electrogenic (creates a small negative membrane potential)
  • Role of ion channels
    • Allows ion movement down electrochemical gradients
    • Permeability of specific ions determines the resting membrane potential
  • Nernst equation: Predicts the equilibrium potential for an ion.
  • Goldman-Hodgkin-Katz equation: Calculates the membrane potential based on the permeability of multiple ions

Resting membrane potential (EM) versus equilibrium potential (Eion)

  • Ionic concentration gradients
  • Selective ionic permeabilities
    • At rest, non-gated K channels are open, with high K+ permeability and low Na+ permeability.
    • K+ efflux is the major contributor to RMP
    • Equilibrium potential for Potassium (EK) is most important at rest.

Equivalent circuit of nerve cell membrane

  • Ohm's law : voltage = current * resistance.
  • Resistance, capacitance, and current relate to ion channel function.

Ion channels as conductors of electricity

  • Ohm's law (V = IR): channels obey Ohm's law (are "ohmic") if their current is directly proportional to voltage; channels don't always follow the law; rectifying channels don't follow Ohm's law and conductance is not constant).

Action Potentials

  • Why? To quickly transmit information over distances (axons, muscle).
  • How? Voltage-gated Na+ and K+ channels; these channels provide the rapid, propagating "all or none" action potential.

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