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What is the primary function of ion channels in the context of nerve impulses?
What is the basis of classification of ion channels?
What is the function of the voltage-sensor domain (VSD) in voltage-gated ion channels?
What type of ion channels are responsible for sensing hot and cold environments in animals?
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What is the function of the selectivity filter in ion channels?
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What is the location of voltage-gated ion channels in neurons?
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What is the consequence of a conformational change in voltage-gated ion channels?
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What is the characteristic of the S4 helix in voltage-gated ion channels?
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What is the structural organization of a voltage-gated ion channel?
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What is the direction of S4 charge movement in response to a change in membrane voltage?
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What is the state of the ion channel between the open and closed states?
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What causes the inactivated state of the ion channel?
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What is the role of voltage-gated sodium channels?
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What type of voltage-gated ion channel plays a role in linking muscle excitation with contraction?
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What is the function of hyperpolarization-activated cyclic nucleotide-gated channels?
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What is the function of voltage-sensitive proton channels?
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What is the primary function of voltage-gated sodium channels in an action potential?
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Which type of ion channels are responsible for membrane repolarization in an action potential?
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What is the primary function of voltage-gated calcium channels (VGCCs)?
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What is the effect of activating L-type VGCCs in cardiac cells?
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Where are P-type VGCCs primarily found?
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What is the effect of activating VGCCs in neurons?
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What is the permeability of VGCCs to Ca+2 compared to Na+?
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What is the effect of activating VGCCs in muscle cells?
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What is the primary function of Ligand-gated ion channels (LGIC) or ionotropic receptors?
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What is the role of T-type channel blockers?
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What is the purpose of the repolarization phase of an action potential?
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What occurs during the depolarization phase of an action potential?
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What is the electrochemical equilibrium for sodium?
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What is the initial phase of an action potential?
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What is the result of the closing of voltage-gated sodium channels?
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What type of ion channels are opened during the overshoot phase of an action potential?
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What happens to the membrane potential during repolarization?
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What is the mechanism of action of Lidocaine?
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What type of disease is cystic fibrosis?
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What is the pharmacological activity of Verapamil?
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What is the name of the gene that encodes the cardiac sodium channel and is associated with Brugada syndrome?
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What is the name of the disease caused by mutations in the KCNA1 gene, which encodes the voltage-gated potassium channel?
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Study Notes
Ion Channels
- Definition: pore-forming membrane proteins associated with the transport of specific ions in or out of the cell.
- Functions:
- Conductance of nerve impulse.
- Generation of action potential.
- Synaptic transmission.
- Cardiac, skeletal, and smooth muscle contraction.
- Controlling the flow of ions across membranes.
Classification of Ion Channels
- Based on the type of ions for which they are permeable.
- Based on the type of stimulus that triggers their activation.
- Classification by stimulus:
- Voltage-gated ion channels: open following a change in the membrane voltage potential.
- Ligand-gated ion channels: allow ions to flow across the pore in response to the binding of a chemical messenger (ligand) to the cytoplasmic or extracellular side of the channel.
- Temperature-gated ion channels: represented by thermo-sensitive ion channels that belong to the transient receptor potential channel family.
- Light-gated ion channels: found in green algae and are named channelrhodopsin-1 and -2.
- Mechanically-gated ion channels: detect mechanical stimulation such as tension, pressure, stretch, and cell volume change.
Voltage-Gated Ion Channels
- Voltage sensitive.
- Conformational change occurs in response to the potential gradient.
- Distributed along the axon and soma of the neurons.
- Structure:
- Each subunit is composed of six transmembrane helices named S1-S6 flanked by intracellular N and C termini.
- S1-S4 forms the voltage-sensor domain (VSD) with a positively charged S4.
- S5-S6 forms the pore domain with the selectivity filter that discriminates the ions.
- Four subunits tetramerize to form an ion channel with a central pore-forming unit surrounded by four VSDs.
- Gating dynamics:
- A voltage-gated ion channel can be in three states: closed, open, or inactivated.
- Opening of the channel pore leads to the flow of ions according to the electrochemical gradient across the membrane.
- The channels go from a closed state (non-conducting) to an open-state (permeable to ions) as a result of a conformational change in the pore.
- Following activation, the channels go through an inactivated state during which the channel is non-conducting and refractory to open, so-called inactivation.
Types of Voltage-Gated Ion Channels
- Voltage-gated sodium channels: responsible for membrane depolarization in action potential.
- Voltage-gated potassium channels: responsible for membrane repolarization in action potential.
- Voltage-gated calcium channels: play an important role in linking muscle excitation with contraction as well as neuronal excitation with neurotransmitter release.
- Hyperpolarization-activated cyclic nucleotide-gated channel: pacemaking channels in the heart, sensitive to cAMP, cGMP that alter the voltage sensitivity of the channels.
- Voltage-sensitive proton channels: strongly pH-regulated that helps in acid extrusion from cell and phagocytosis.
Voltage-Gated Sodium Channels
- Expressed in all excitable tissues.
- Responsible for the rapid membrane depolarization during the action potential.
- Activation and inactivation are voltage-dependent, very fast processes (1-10 ms).
- Important targets for drugs, e.g., local anesthetics.
Voltage-Gated Potassium Channels
- Found in almost all living organisms.
- Conduct rapidly and selectively K+ ions down their electrochemical gradient.
- Responsible for membrane repolarization in action potential.
- One of the key components in generation and propagation of electrical impulses in nervous system and in the heart.
Voltage-Gated Calcium Channels (VGCCs)
- Found in the membrane of excitable cells as muscle, glial cells, and neurons with a permeability to Ca+2.
- Slightly permeable to Na+ (also called Ca+2-Na+ channels), but their permeability to Ca+2 is about 1000-fold greater.
- At resting membrane potential, VGCCs are normally closed.
- Activated (opened) at depolarized membrane potentials.
- Activation of particular VGCCs allows Ca+2 to rush into the cell, which depending on the cell type, results in:
- Activation of calcium-sensitive potassium channels.
- Muscular contraction.
- Excitation of neurons.
- Up-regulation of gene expression.
- Or release of hormones or neurotransmitters.
Types of VGCCs
- L-type: found in skeletal muscle, smooth muscle, bone, ventricular myocytes (responsible for prolonged action potential in cardiac cell), dendrites and dendritic spines of cortical neurons.
- P-type: found in Purkinje neurons in the cerebellum and cerebellar granule cells.
- N-type: found throughout the brain and peripheral nervous system.
- R-type: found in cerebellar granule cells and other neurons.
- T-type: found in neurons, bone.
Ligand-Gated Ion Channels (LGIC) or Ionotropic Receptors
- A group of transmembrane ion-channel proteins which open to allow ions to pass through the membrane in response to the binding of a chemical messenger (ligand) such as a neurotransmitter.
- Structure: two domains; transmembrane domain including channel pore and extracellular domain including ligand binding site.
- Function: conversion of presynaptic chemical signal into post-synaptic electrical signal to elicit a cellular response.
- Examples: receptors for acetylcholine and glutamate.
Biological Implications of Ion Channels
- Action potential:
- Definition: nerve signals.
- Phases: hypopolarization, depolarization, overshoot, repolarization, and hyperpolarization.
- Therapeutic applications:
- Different medical conditions have been attributed to ion channel dysfunction.
- Examples for drugs targeting ion channels:
- Lidocaine: local anesthetic, sodium channel blocker.
- Verapamil: antihypertensive, calcium channel blocker.
- Ion channel dysfunction and diseases:
- Channelopathies: diseases caused by disturbed function of ion channel subunits or the proteins that regulate them.
- Examples:
- Cystic fibrosis: caused by mutations in the CFTR gene, which encodes the chloride channel.
- Brugada syndrome: a ventricular arrhythmia caused by mutation in SCN5A, which encodes the cardiac sodium channel.
- Episodic ataxia: caused by mutations in KCNA1 gene, which encodes the voltage-gated potassium channel.
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Description
This quiz covers the definition and functions of ion channels, including conducting nerve impulses, generating action potentials, and controlling ion flow across membranes.
