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Questions and Answers
What is primarily responsible for the gating of voltage-gated ion channels?
What is primarily responsible for the gating of voltage-gated ion channels?
Channel modulation can last for only a few seconds.
Channel modulation can last for only a few seconds.
False
Name one example of a ligand-gated channel.
Name one example of a ligand-gated channel.
Ach (Acetylcholine) or GABA
The process that alters the channel gating in response to factors like second messengers is called ______.
The process that alters the channel gating in response to factors like second messengers is called ______.
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Match the ion channel type with their gating control factor:
Match the ion channel type with their gating control factor:
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What happens to ion channels when they transition from an open state to a non-conducting state?
What happens to ion channels when they transition from an open state to a non-conducting state?
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Ion channels conduct only their permeating ion and exclude foreign molecules.
Ion channels conduct only their permeating ion and exclude foreign molecules.
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What factors control the gating process of ion channels?
What factors control the gating process of ion channels?
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What does the term 'Equilibrium Potential' refer to?
What does the term 'Equilibrium Potential' refer to?
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The Potassium Equilibrium Potential for a typical neuron is more positive than the resting membrane potential.
The Potassium Equilibrium Potential for a typical neuron is more positive than the resting membrane potential.
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What is the resting membrane potential (RMP) for a typical neuron?
What is the resting membrane potential (RMP) for a typical neuron?
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The movement of ions down their concentration gradient occurs when channels are __________ to specific ions.
The movement of ions down their concentration gradient occurs when channels are __________ to specific ions.
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Match the following concepts with their correct descriptions:
Match the following concepts with their correct descriptions:
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What is the primary purpose of voltage-gated sodium channels during an action potential?
What is the primary purpose of voltage-gated sodium channels during an action potential?
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During the resting state of a neuron, Na+ permeability is significantly higher than K+ permeability.
During the resting state of a neuron, Na+ permeability is significantly higher than K+ permeability.
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What does the term 'selectivity' refer to in the context of ion channels?
What does the term 'selectivity' refer to in the context of ion channels?
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The ratio of permeabilities during the rest in the squid giant axon is PK:PNa:PCl = _____: _____: _____
The ratio of permeabilities during the rest in the squid giant axon is PK:PNa:PCl = _____: _____: _____
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Match the following patch clamp configurations with their descriptions:
Match the following patch clamp configurations with their descriptions:
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What mechanism primarily controls the opening and closing of ion channels?
What mechanism primarily controls the opening and closing of ion channels?
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Ion channels are always in the open state, allowing continuous ion flow.
Ion channels are always in the open state, allowing continuous ion flow.
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What happens during the inactivation of ion channels?
What happens during the inactivation of ion channels?
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During the depolarizing phase of an action potential, the permeability ratio is PK:PNa:PCl = _____: _____: _____
During the depolarizing phase of an action potential, the permeability ratio is PK:PNa:PCl = _____: _____: _____
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Which recording technique allows the measurement of ionic currents while controlling the membrane potential of a cell?
Which recording technique allows the measurement of ionic currents while controlling the membrane potential of a cell?
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What process allows a channel to return to a closed state?
What process allows a channel to return to a closed state?
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Inactivation occurs due to depolarization and leads to a non-conducting state.
Inactivation occurs due to depolarization and leads to a non-conducting state.
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What structural feature of voltage-gated ion channels is primarily responsible for ion selectivity?
What structural feature of voltage-gated ion channels is primarily responsible for ion selectivity?
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The S4 helix is responsive to an increase in intracellular membrane __________.
The S4 helix is responsive to an increase in intracellular membrane __________.
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Which amino acid motif is crucial for the fast inactivation of sodium channels?
Which amino acid motif is crucial for the fast inactivation of sodium channels?
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Match each channel type with its corresponding primary function:
Match each channel type with its corresponding primary function:
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The gating current is associated with ion movement within the ion channel structure.
The gating current is associated with ion movement within the ion channel structure.
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What prevents sustained ion flow through the sodium channel during inactivation?
What prevents sustained ion flow through the sodium channel during inactivation?
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The carbonyl backbone groups of the __________ motif in the P loop determine the ion selectivity for Kv channels.
The carbonyl backbone groups of the __________ motif in the P loop determine the ion selectivity for Kv channels.
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What does the movement of the S4 helix in voltage-gated ion channels lead to?
What does the movement of the S4 helix in voltage-gated ion channels lead to?
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Study Notes
Membrane Potential Fundamentals
- Cells have a membrane potential (RMP) typically between -70 and 40 mV
- This is due to ion concentration gradients and ion permeability across the membrane
- Extracellular concentrations of Na+, Cl-, and other ions differ from intracellular concentrations
- The RMP is primarily determined by the K+ concentration gradient
- The K+ concentration is much higher inside the cells than outside
- Ion channels such as voltage-gated channels control ion movement across the membrane
- Changes in ion movement across the membrane can be exploited by the cell to effect changes in cellular events
Equilibrium Potential
- Equilibrium potential is the membrane potential at which there is no net movement of an ion across the membrane
- Equilibrium potential is determined by the Nernst equation
- It considers the concentration gradient and the electrical gradient of an ion
- The Nernst equation calculates the equilibrium potential and gives the result in mV
- The different ions can be described as being at equilibrium under different conditions/states determined by the Nernst equation
Potassium Equilibrium
- For a typical neuron, extracellular K+ concentration is 5 mM and intracellular K+ concentration is 100 mM
- The resting membrane potential (RMP) is -70 mV
- The concentration gradient would cause K+ efflux
- The electrical gradient would cause K+ influx, which happens at rest
- The equilibrium potential (Ek) for K+ is usually about -80 mV
- The fact that the RMP is -70 mV and not -80 mV implies membrane permeability to other ions
- The RMP is a balance between permeability to these other ions (Na+, Cl-)
How the RMP is established
- Most mammalian cells have RMPs that are slightly more positive than the K+ equilibrium potential (as there is always some leakage pathway)
- Na+ and Cl- permeabilities contribute to the RMP
- The extent to which an ion contributes to the RMP is relative to the permeability of the membrane to that ion
- Even large concentration gradients can have little impact on the RMP when the ion permeability is low
Importance of RMP
- Rapid changes in the ratios of ion permeability are the basis for bioelectric phenomena
- These changes underlie neuronal action potentials
- Alterations in permeability underlie subthreshold and suprathreshold potentials.
Physiology of Voltage-Gated Ion Channels
- Voltage-gated channels open/close depending on the membrane potential
- Ion (e.g., Na+, Ca^2+, K+) flows into or out of the cell
- The initial membrane potential change causes a cascade of effects, which involves the movement of charge in the channel structures
Single Channel Recording
- Patch clamp technique allows the study of individual ion channel activity
- Nobel Laureates Erwin Neher and Bert Sakmann received the Nobel Prize for Medicine in 1991 for this work
Methods for Recording Ionic Currents
- Two-electrode voltage clamp is a method for measuring ionic currents
- Different patch-clamp configurations exist (e.g., cell-attached, whole-cell, inside-out, outside-out)
Properties of Ion Channels - Selectivity, Gating, and Inactivation
- Ion channels select which ions they permit to pass
- Channel selectivity is determined by the structure of the pore
- Gating describes how the channels' open and close states are regulated
- Inactivation is a process, in which, once an ion channel is open there are various routes back to a non-conducting state; one mechanism is deactivation (driven by repolarization) and another is inactivation (driven by sustained depolarization)
Features of Voltage-Gated Ion Channels
- Voltage-gated ion channels (e.g., Na+, K+, Ca2+) have a specific selectivity filter and a voltage sensor
Structures of Voltage-Activated Ion Channels
- Channels composed of multiple subunits (e.g. α-subunit) have specific transmembrane structures (e.g. S4 helix) that participate in ion channel activation and inactivation
Selectivity Filter: The Pore Loop
- Pore loop plays a role in ion selectivity; ion selectivity is determined by carbonyl backbone groups of the TVGYG motif in the pore loop
- For example, Nav channels have specific DEKA side chains.
Ion Channel Structure - Ion Selectivity
- Details about the channel structure in terms of folds and how selectivity related to location in water vs within the pore
- Figures show the differences in how Na+ and K+ ions interact within the channel
- Specific structural components in ion channel structure relate to ion selectivity
Gating - The Voltage Sensor
- Detailed structure of the S4 transmembrane helix including its positively charged amino acids
- These positively charged amino acids are responsible for the voltage-sensing properties of the channel
- This mechanism of voltage sensing relates to the opening of the channel allowing ions within the membrane to carry current
Voltage-Activated Sodium Channels - Gating
- Sodium channel activation is associated with charge movement within the channel
- The movement through the structures is known as the gating current
- This charge movement precedes ion flow
Inactivation - The IFM Motif for NaV Channels
- Fast inactivation of Na+ channels is mediated by an intracellular 'gate' that binds to the intracellular mouth of the pore
- The IFM motif is a hydrophobic triad that forms the inactivation gate and is part of a tethered pore blocker
- The IFM peptide occludes the Na+ channel pore to stop ion flow
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Description
This quiz covers the basics of membrane potential, including resting membrane potential (RMP) and equilibrium potential. It explores the roles of ion concentration gradients and permeability, particularly focusing on potassium ions. Additional concepts such as the Nernst equation will also be examined.
