Ion Channels and Their Functions

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Questions and Answers

What is the primary function of ion channels in the context of nerve impulses?

To control the flow of ions across membranes

To conduct nerve impulses (correct)

To facilitate synaptic transmission

To generate action potential

What is the basis of classification of ion channels?

Location of the ion channel in the cell

Type of ions for which they are permeable

Structure of the ion channel

Type of stimulus that triggers their activation (correct)

What is the function of the voltage-sensor domain (VSD) in voltage-gated ion channels?

To detect mechanical stimulation

To respond to changes in membrane voltage potential (correct)

To form the pore domain

To sense changes in temperature

What type of ion channels are responsible for sensing hot and cold environments in animals?

Temperature-gated ion channels Signup and view all the answers

What is the function of the selectivity filter in ion channels?

To discriminate between different ions Signup and view all the answers

What is the location of voltage-gated ion channels in neurons?

Distributed along the axon and soma Signup and view all the answers

What is the consequence of a conformational change in voltage-gated ion channels?

The ion channel opens Signup and view all the answers

What is the characteristic of the S4 helix in voltage-gated ion channels?

It is positively charged Signup and view all the answers

What is the structural organization of a voltage-gated ion channel?

Four subunits tetramerizing to form a central pore-forming unit surrounded by four VSDs Signup and view all the answers

What is the direction of S4 charge movement in response to a change in membrane voltage?

Outward direction Signup and view all the answers

What is the state of the ion channel between the open and closed states?

Inactivated Signup and view all the answers

What causes the inactivated state of the ion channel?

Physical blockage by a 'ball' of amino acids Signup and view all the answers

What is the role of voltage-gated sodium channels?

Membrane depolarization in action potential Signup and view all the answers

What type of voltage-gated ion channel plays a role in linking muscle excitation with contraction?

Voltage-gated calcium channels Signup and view all the answers

What is the function of hyperpolarization-activated cyclic nucleotide-gated channels?

Pacemaking in the heart Signup and view all the answers

What is the function of voltage-sensitive proton channels?

Acid extrusion from cells and phagocytosis Signup and view all the answers

What is the primary function of voltage-gated sodium channels in an action potential?

Depolarization of the membrane Signup and view all the answers

Which type of ion channels are responsible for membrane repolarization in an action potential?

Voltage-gated potassium channels Signup and view all the answers

What is the primary function of voltage-gated calcium channels (VGCCs)?

Permeability to Ca+2 and Na+ Signup and view all the answers

What is the effect of activating L-type VGCCs in cardiac cells?

Prolonged action potential Signup and view all the answers

Where are P-type VGCCs primarily found?

Purkinje neurons in the cerebellum Signup and view all the answers

What is the effect of activating VGCCs in neurons?

Excitation of neurons Signup and view all the answers

What is the permeability of VGCCs to Ca+2 compared to Na+?

1000-fold greater Signup and view all the answers

What is the effect of activating VGCCs in muscle cells?

Muscular contraction Signup and view all the answers

What is the primary function of Ligand-gated ion channels (LGIC) or ionotropic receptors?

To convert presynaptic chemical signal into post-synaptic electrical signal Signup and view all the answers

What is the role of T-type channel blockers?

To act as antiepileptic and neuropathic painkiller drugs Signup and view all the answers

What is the purpose of the repolarization phase of an action potential?

To restore the resting membrane potential Signup and view all the answers

What occurs during the depolarization phase of an action potential?

A large influx of sodium ions Signup and view all the answers

What is the electrochemical equilibrium for sodium?

+61 mV Signup and view all the answers

What is the initial phase of an action potential?

Hypopolarization Signup and view all the answers

What is the result of the closing of voltage-gated sodium channels?

Repolarization Signup and view all the answers

What type of ion channels are opened during the overshoot phase of an action potential?

Voltage-gated potassium channels Signup and view all the answers

What happens to the membrane potential during repolarization?

It becomes more negative than the default membrane potential Signup and view all the answers

What is the mechanism of action of Lidocaine?

Sodium channel blocker Signup and view all the answers

What type of disease is cystic fibrosis?

Channelopathy Signup and view all the answers

What is the pharmacological activity of Verapamil?

Antihypertensive Signup and view all the answers

What is the name of the gene that encodes the cardiac sodium channel and is associated with Brugada syndrome?

SCN5A Signup and view all the answers

What is the name of the disease caused by mutations in the KCNA1 gene, which encodes the voltage-gated potassium channel?

Episodic ataxia Signup and view all the answers

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.