Ion channel - AbsoluteAstronomy.com

Ion channels are pore-forming protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s that help establish and control the small voltage

Voltage

Voltage, otherwise known as electrical potential difference or electric tension is the difference in electric potential between two points — or the difference in electric potential energy per unit charge between two points...

gradient

Gradient

In vector calculus, the gradient of a scalar field is a vector field that points in the direction of the greatest rate of increase of the scalar field, and whose magnitude is the greatest rate of change....

across the plasma membrane of cell

Cell (biology)

The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

s (see cell potential) by allowing the flow of ion

Ion

An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...

s down their electrochemical gradient

Electrochemical gradient

An electrochemical gradient is a spatial variation of both electrical potential and chemical concentration across a membrane; that is, a combination of the membrane potential and the pH gradient...

. They are present in the membrane

Cell membrane

The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

s that surround all biological cells. The study of ion channels involves many scientific techniques such as voltage clamp

Voltage clamp

The voltage clamp is used by electrophysiologists to measure the ion currents across the membrane of excitable cells, such as neurons, while holding the membrane voltage at a set level. Cell membranes of excitable cells contain many different kinds of ion channels, some of which are voltage gated...

electrophysiology

Electrophysiology

Electrophysiology is the study of the electrical properties of biological cells and tissues. It involves measurements of voltage change or electric current on a wide variety of scales from single ion channel proteins to whole organs like the heart...

(in particular patch clamp

Patch clamp

The patch clamp technique is a laboratory technique in electrophysiology that allows the study of single or multiple ion channels in cells. The technique can be applied to a wide variety of cells, but is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle...

), immunohistochemistry

Immunohistochemistry

Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...

, and RT-PCR.

Basic features

Ion channels regulate the flow of ions across the membrane in all cells. Ion channels are integral membrane protein

Integral membrane protein

An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...

s; or, more typically, an assembly of several proteins. They are present on all membranes of cell (plasma membrane) and intracellular organelles (nucleus, mitochondria, endoplasmic reticulum, golgi apparatus and so on). Such "multi-subunit

Protein subunit

In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...

" assemblies usually involve a circular arrangement of identical or homologous

Homology (biology)

Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

proteins closely packed around a water-filled pore through the plane of the membrane or lipid bilayer

Lipid bilayer

The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...

. For most voltage-gated ion channel

Voltage-gated ion channel

Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....

s, the pore-forming subunit(s) are called the α subunit, while the auxiliary subunits are denoted β, γ, and so on. Some channels permit the passage of ions based solely on their charge of positive (cation) or negative (anion). However, the archetypal channel pore is just one or two atoms wide at its narrowest point and is selective for specific species of ion, such as sodium

Sodium

Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

or potassium

Potassium

Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

. These ions move through the channel pore single file nearly as quickly as the ions move through free fluid. In some ion channels, passage through the pore is governed by a "gate," which may be opened or closed by chemical or electrical signals, temperature, or mechanical force, depending on the variety of channel.

Biological role

Because channels underlie the nerve impulse and because "transmitter-activated" channels mediate conduction across the synapse

Synapse

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

s, channels are especially prominent components of the nervous system

Nervous system

The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

. Indeed, most of the offensive and defensive toxins that organisms have evolved for shutting down the nervous systems of predators and prey (e.g., the venoms produced by spiders, scorpions, snakes, fish, bees, sea snails and others) work by modulating ion channel conductance and/or kinetics. In addition, ion channels are key components in a wide variety of biological processes that involve rapid changes in cells, such as cardiac

Cardiac muscle

Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...

, skeletal

Skeletal muscle

Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

, and smooth muscle

Smooth muscle

Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

contraction

Muscle contraction

Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...

, epithelial

Epithelium

Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

transport of nutrients and ions, T-cell activation and pancreatic

Pancreas

The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

beta-cell insulin

Insulin

Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

release. In the search for new drugs, ion channels are a frequent target.

Diversity

There are over 300 types of ion channels in a living cell. Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, the number of gates (pores) and localization of proteins.

Further heterogeneity of ion channels arises when channels with different constitutive subunits

Protein subunit

give rise to a specific kind of current. Absence or mutation of one or more of the contributing types of channel subunits can result in loss of function and, potentially, underlie neurologic diseases.

By gating

Ion channels may be classified by gating, i.e. what opens and closes the channels. Voltage-gated ion channels open or close depending on the voltage gradient across the plasma membrane, while ligand-gated ion channels open or close depending on binding of ligands

Ligand (biochemistry)

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

to the channel.

Voltage-gated

Voltage-gated ion channels open and close in response to membrane potential

Membrane potential

Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

Voltage-gated sodium channels: This family contains at least 9 members and is largely responsible for action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

creation and propagation. The pore-forming α subunits are very large (up to 4,000 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s) and consist of four homologous repeat domains (I-IV) each comprising six transmembrane segments (S1-S6) for a total of 24 transmembrane segments. The members of this family also coassemble with auxiliary β subunits, each spanning the membrane once. Both α and β subunits are extensively glycosylated
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

.

Voltage-gated calcium channels: This family contains 10 members, though these members are known to coassemble with α₂δ, β, and γ subunits. These channels play an important role in both linking muscle excitation with contraction as well as neuronal excitation with transmitter release. The α subunits have an overall structural resemblance to those of the sodium channels and are equally large.
- Cation channels of sperm
  Cation channels of sperm
  The cation channels of sperm also known as Catsper channels or CatSper, are ion channels that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca2+ channels that seem to be specific to sperm. These channels are required...
  
  : This small family of channels, normally referred to as Catsper channels, is related to the two-pore channels and distantly related to TRP channels.

Voltage-gated potassium channel
Voltage-gated potassium channel
Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....

s (K_V): This family contains almost 40 members, which are further divided into 12 subfamilies. These channels are known mainly for their role in repolarizing the cell membrane following action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

s. The α subunits have six transmembrane segments, homologous to a single domain of the sodium channels. Correspondingly, they assemble as tetramers to produce a functioning channel.

Some transient receptor potential channels: This group of channels, normally referred to simply as TRP channels, is named after their role in Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

phototransduction. This family, containing at least 28 members, is incredibly diverse in its method of activation. Some TRP channels seem to be constitutively open, while others are gated by voltage
Voltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....

, intracellular Ca²⁺, pH, redox state, osmolarity, and mechanical stretch
Stretch-activated ion channel
Stretch-activated or stretch-gated ion channels are ion channels which open their pores in response to mechanical deformation of a neuron's plasma membrane. Stretch-activated channels were first observed in chick skeletal muscles by Falguni Guharay and Frederick Sachs in 1983 and the results were...

. These channels also vary according to the ion(s) they pass, some being selective for Ca²⁺ while others are less selective, acting as cation channels. This family is subdivided into 6 subfamilies based on homology: classical (TRPC
TRPC
TRPC is a family of transient receptor potential cation channels in animals.TRPC channels form the subfamily of channels in human most closely related to drosophila TRP channels. In terms of structure, this family possesses a number of similar characteristics...

), vanilloid receptors (TRPV
TRPV
TRPV is a family of transient receptor potential ion channels. These channels are selective for calcium and magnesium over sodium ions. Like other members of the TRP superfamily, TRPV channels can be activated through seemingly disparate mechanisms...

), melastatin (TRPM
TRPM
TRPM is a family of transient receptor potential ion channels . Functional TRPM channels are believed to form tetramers....

), polycystins (TRPP
TRPP
TRPP is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease.-Subcategories:...

), mucolipins (TRPML
TRPML
TRPML comprises a group of three evolutionary related proteins that belongs to the large family of transient receptor potential ion channels...

), and ankyrin transmembrane protein 1 (TRPA
TRPA (channel)
TRPA is a family of transient receptor potential ion channels.The sole member of the TRPA sub-family, TRPA1, contains 14 N-terminal ankyrin repeats and is believed to function as a mechanical stress sensor. It is expressed in the dorsal root ganglion, trigeminal ganglion, and hair cells...

).

Hyperpolarization-activated cyclic nucleotide-gated channels: The opening of these channels is due to hyperpolarization
Hyperpolarization (biology)
Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization.Hyperpolarization is often caused by efflux of K+ through K+ channels, or influx of Cl– through Cl– channels. On the other hand, influx of cations, e.g...

rather than the depolarization required for other cyclic nucleotide-gated channels. These channels are also sensitive to the cyclic nucleotides cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...

and cGMP
Cyclic guanosine monophosphate
Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP...

, which alter the voltage sensitivity of the channel’s opening. These channels are permeable to the monovalent cations K⁺ and Na⁺. There are 4 members of this family, all of which form tetramers of six-transmembrane α subunits. As these channels open under hyperpolarizing conditions, they function as pacemaking
Cardiac pacemaker
right|thumb|350px|Image showing the cardiac pacemaker which is the SA nodeThe contraction of heart muscle in all animals with hearts is initiated by chemical impulses. The rate at which these impulses fire controls the heart rate...

channels in the heart, particularly the SA node.

Voltage-gated proton channel
Voltage-gated proton channel
Voltage-gated proton channels are ion channels that have the unique property of opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells...

s: Voltage-gated proton channels open with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when the electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from cells. Another important function occurs in phagocytes (e.g. eosinophils, neutrophils, macrophages) during the "respiratory burst." When bacteria or other microbes are engulfed by phagocytes, the enzyme NADPH oxidase
NADPH oxidase
The NADPH oxidase is a membrane-bound enzyme complex. It can be found in the plasma membrane as well as in the membrane of phagosome.-Subunits:It is made up of six subunits...

assembles in the membrane and begins to produce reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

(ROS) that help kill bacteria. NADPH oxidase is electrogenic, moving electrons across the membrane, and proton channels open to allow proton flux to balance the electron movement electrically.

Ligand-gated

Also known as ionotropic receptors

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

, this group of channels open in response to specific ligand molecules binding to the extracellular domain of the receptor protein. Ligand binding causes a conformational change in the structure of the channel protein that ultimately leads to the opening of the channel gate and subsequent ion flux across the plasma membrane. Examples of such channels include the cation-permeable "nicotinic" Acetylcholine receptor

Acetylcholine receptor

An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...

, ionotropic glutamate-gated receptors and ATP-gated P2X receptors, and the anion-permeable γ-aminobutyric acid-gated GABA_A receptor

GABA receptor

The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...

.

Ion channels activated by second messengers may also be categorized in this group, although ligands

Ligand (biochemistry)

and second messengers are otherwise distinguished from each other.

Other gating

Other gating include activation/inactivation by e.g. second messengers from the inside of the cell membrane

Cell membrane

, rather as from outside, as in the case for ligands. Ions may count to such second messengers, and then causes direct activation, rather than indirect, as in the case were the electric potential of ions cause activation/inactivation of voltage-gated ion channels.

Some potassium channels
- Inward-rectifier potassium channels
  Inward-rectifier potassium ion channel
  Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
  
  : These channels allow potassium to flow into the cell in an inwardly rectifying manner, i.e., potassium flows effectively into, but not out of, the cell. This family is composed of 15 official and 1 unofficial members and is further subdivided into 7 subfamilies based on homology. These channels are affected by intracellular ATP
  Adenosine triphosphate
  Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
  
  , PIP₂, and G-protein βγ subunits. They are involved in important physiological processes such as the pacemaker activity in the heart, insulin release, and potassium uptake in glial cells. They contain only two transmembrane segments, corresponding to the core pore-forming segments of the K_V and K_Ca channels. Their α subunits form tetramers.
- Calcium-activated potassium channel
  Calcium-activated potassium channel
  Calcium-activated potassium channels are divided into BK channels, IK channels, and SK channels based on their conductance ....
  
  s: This family of channels is, for the most part, activated by intracellular Ca²⁺ and contains 8 members.
- Two-pore-domain potassium channels
  Tandem pore domain potassium channel
  The two-pore-domain potassium channel is a family of 15 members form what is known as "leak channels" which possess Goldman-Hodgkin-Katz rectification. These channels are regulated by several mechanisms including oxygen tension, pH, mechanical stretch, and G-proteins...
  
  : This family of 15 members form what is known as leak channels, and they follow Goldman-Hodgkin-Katz
  GHK current equation
  The Goldman–Hodgkin–Katz flux equation describes the ionic flux carried by an ionic species across a cell membrane as a function of the transmembrane potential and the concentrations of the ion inside and outside of the cell...
  
  (open) rectification
  Rectifier
  A rectifier is an electrical device that converts alternating current , which periodically reverses direction, to direct current , which flows in only one direction. The process is known as rectification...
  
  .

Light-gated channels like channelrhodopsin
Channelrhodopsin
Channelrhodopsins are a subfamily of opsin proteins that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis, i.e. movement in response to light. Expressed in cells of other organisms, they enable the use of light to control...

are directly opened by the action of light.

Mechanosensitive ion channel
Mechanosensitive ion channel
Mechanosensitive channels are found in a number of tissues and organisms and are thought to be the sensors for a number of systems including the senses of touch, hearing and balance, as well as participating in cardiovascular regulation and osmotic homeostasis...

s are opening under the influence of stretch, pressure, shear, displacement.

Cyclic nucleotide-gated channels: This superfamily of channels contains two families: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. It should be noted that this grouping is functional rather than evolutionary.
- Cyclic nucleotide-gated channels: This family of channels is characterized by activation due to the binding of intracellular cAMP
  Cyclic adenosine monophosphate
  Cyclic adenosine monophosphate is a second messenger important in many biological processes...
  
  or cGMP
  Cyclic guanosine monophosphate
  Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP...
  
  , with specificity varying by member. These channels are primarily permeable to monovalent cations such as K⁺ and Na⁺. They are also permeable to Ca²⁺, though it acts to close them. There are 6 members of this family, which is divided into 2 subfamilies.
- Hyperpolarization-activated cyclic nucleotide-gated channels

Temperature Gated Channels: Members of the Transient Receptor Potential ion channel superfamily, such as TRPV1
TRPV1
The transient receptor potential cation channel subfamily V member 1 ', also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene...

or TRPM8
TRPM8
Transient receptor potential cation channel subfamily M member 8 , also known as the cold and menthol receptor 1 , is a protein that in humans is encoded by the TRPM8 gene.-Function:...

are opened either by hot or cold temperatures.

By ions

Chloride channel
Chloride channel
Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members.Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell...

s: This superfamily of poorly-understood channels consists of approximately 13 members. They include ClCs, CLICs, Bestrophins and CFTRs. These channels are non-selective for small anions; however chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...

is the most abundant anion, and hence they are known as chloride channels.

Potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...

s
- Voltage-gated potassium channel
  Voltage-gated potassium channel
  Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....
  
  s e.g., Kvs, Kirs etc.
- Calcium-activated potassium channel
  Calcium-activated potassium channel
  Calcium-activated potassium channels are divided into BK channels, IK channels, and SK channels based on their conductance ....
  
  s e.g., BKCa or MaxiK, SK, etc.
- Inward-rectifier potassium channels
  Inward-rectifier potassium ion channel
  Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
- Two-pore-domain potassium channels: This family of 15 members form what is known as leak channels, and they follow Goldman-Hodgkin-Katz
  GHK current equation
  The Goldman–Hodgkin–Katz flux equation describes the ionic flux carried by an ionic species across a cell membrane as a function of the transmembrane potential and the concentrations of the ion inside and outside of the cell...
  
  (open) rectification
  Rectifier
  A rectifier is an electrical device that converts alternating current , which periodically reverses direction, to direct current , which flows in only one direction. The process is known as rectification...
  
  .

Sodium channels
- voltage-gated sodium channels NaVs
- epithelial sodium channel
  Epithelial sodium channel
  The epithelial sodium channel is a membrane-bound ion-channel that is permeable for Li+-ions, protons and especially Na+-ions. It is a constitutively active ion-channel...
  
  s (ENaC)

Calcium channel
Calcium channel
A Calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels.-Comparison tables:...

s CaVs

Proton channels
- Voltage-gated proton channels

Non-selective cation channels: These let many types of cations, mainly Na⁺, K⁺ and Ca²⁺ through the channel.
- Most Transient receptor potential channels
  Transient receptor potential
  Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other...

Other classifications

There are other types of ion channel classifications that are based on less normal characteristics, e.g. multiple pores and transient potentials.

Almost all ion channels have one single pore. However, there are also those with two:

Two-pore channel
Two-pore channel
'Two-pore channels: This small family of 2 members putatively forms cation-selective ion channels. They are predicted to contain two KV-style six-transmembrane domains, suggesting they form a dimer in the membrane. These channels are closely related to CatSper channels and, more distantly, to TRP...

s: This small family of 2 members putatively forms cation-selective ion channels. They are predicted to contain two K_V-style six-transmembrane domains, suggesting they form a dimer in the membrane. These channels are related to catsper channels
Cation channels of sperm
The cation channels of sperm also known as Catsper channels or CatSper, are ion channels that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca2+ channels that seem to be specific to sperm. These channels are required...

channels and, more distantly, TRP
Transient receptor potential
Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other...

channels.

There are channels that are classified by the duration of the response to stimuli:

Transient receptor potential channels: This group of channels, normally referred to simply as TRP channels, is named after their role in Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

phototransduction. This family, containing at least 28 members, is incredibly diverse in its method of activation. Some TRP channels seem to be constitutively open, while others are gated by voltage
Voltage-gated ion channel
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells....

, intracellular Ca²⁺, pH, redox state, osmolarity, and mechanical stretch
Stretch-activated ion channel
Stretch-activated or stretch-gated ion channels are ion channels which open their pores in response to mechanical deformation of a neuron's plasma membrane. Stretch-activated channels were first observed in chick skeletal muscles by Falguni Guharay and Frederick Sachs in 1983 and the results were...

. These channels also vary according to the ion(s) they pass, some being selective for Ca²⁺ while others are less selective, acting as cation channels. This family is subdivided into 6 subfamilies based on homology: canonical (TRPC
TRPC
TRPC is a family of transient receptor potential cation channels in animals.TRPC channels form the subfamily of channels in human most closely related to drosophila TRP channels. In terms of structure, this family possesses a number of similar characteristics...

), vanilloid receptors (TRPV
TRPV
TRPV is a family of transient receptor potential ion channels. These channels are selective for calcium and magnesium over sodium ions. Like other members of the TRP superfamily, TRPV channels can be activated through seemingly disparate mechanisms...

), melastatin (TRPM
TRPM
TRPM is a family of transient receptor potential ion channels . Functional TRPM channels are believed to form tetramers....

), polycystins (TRPP
TRPP
TRPP is a family of transient receptor potential ion channels which when mutated can cause polycystic kidney disease.-Subcategories:...

), mucolipins (TRPML
TRPML
TRPML comprises a group of three evolutionary related proteins that belongs to the large family of transient receptor potential ion channels...

), and ankyrin transmembrane protein 1 (TRPA
TRPA (channel)
TRPA is a family of transient receptor potential ion channels.The sole member of the TRPA sub-family, TRPA1, contains 14 N-terminal ankyrin repeats and is believed to function as a mechanical stress sensor. It is expressed in the dorsal root ganglion, trigeminal ganglion, and hair cells...

).

Detailed structure

Channels differ with respect to the ion they let pass (for example, Na⁺, K⁺, Cl⁻), the ways in which they may be regulated, the number of subunits of which they are composed and other aspects of structure. Channels belonging to the largest class, which includes the voltage-gated channels that underlie the nerve impulse, consists of four subunits with six transmembrane helices

Transmembrane helix

Transmembrane domain usually denotes a single transmembrane alpha helix of a transmembrane protein. It is called a "domain" because an alpha-helix in a membrane can fold independently from the rest of the protein, similar to domains of water-soluble proteins...

each. On activation, these helices move about and open the pore. Two of these six helices are separated by a loop that lines the pore and is the primary determinant of ion selectivity and conductance in this channel class and some others. The existence and mechanism for ion selectivity was first postulated in the 1960s by Clay Armstrong

Clay Armstrong

Clay Margarave Armstrong is an American physiologist and a former student of Dr. Andrew Fielding Huxley. He is currently a professor of Physiology at the University of Pennsylvania....

. He suggested that the pore lining could efficiently replace the water molecules that normally shield potassium ions, but that sodium ions were too small to allow such shielding, and therefore could not pass through. This mechanism was finally confirmed when the structure of the channel was elucidated. The channel subunits of one such other class, for example, consist of just this "P" loop and two transmembrane helices. The determination of their molecular structure by Roderick MacKinnon

Roderick MacKinnon

Roderick MacKinnon is a professor of Molecular Neurobiology and Biophysics at Rockefeller University who won the Nobel Prize in Chemistry together with Peter Agre in 2003 for his work on the structure and operation of ion channels....

using X-ray crystallography

Crystallography

Crystallography is the experimental science of the arrangement of atoms in solids. The word "crystallography" derives from the Greek words crystallon = cold drop / frozen drop, with its meaning extending to all solids with some degree of transparency, and grapho = write.Before the development of...

won a share of the 2003 Nobel Prize in Chemistry

Nobel Prize in Chemistry

The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...

.

Because of their small size and the difficulty of crystallizing integral membrane proteins for X-ray analysis, it is only very recently that scientists have been able to directly examine what channels "look like." Particularly in cases where the crystallography required removing channels from their membranes with detergent, many researchers regard images that have been obtained as tentative. An example is the long-awaited crystal structure of a voltage-gated potassium channel, which was reported in May 2003. One inevitable ambiguity about these structures relates to the strong evidence that channels change conformation as they operate (they open and close, for example), such that the structure in the crystal could represent any one of these operational states. Most of what researchers have deduced about channel operation so far they have established through electrophysiology

Electrophysiology

, biochemistry

Biochemistry

Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...

, gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

sequence comparison and mutagenesis

Mutagenesis

Mutagenesis is a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures...

.

Channels can have single (CLICs) to multiple transmembrane (K channels, P2X receptors, Na channels) domains which span plasma membrane to form pores. Pore can determine the selectivity of the channel. Gate can be formed either inside or outside the pore region.

Diseases of ion channels

There are a number of chemicals and genetic disorders which disrupt normal functioning of ion channels and have disastrous consequences for the organism. Genetic disorders of ion channels and their modifiers are known as Channelopathies

Channelopathy

Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them. These diseases may be either congenital or acquired .There are a large number of distinct dysfunctions known to be caused by ion channel...

. See :Category:Channelopathy for a full list.

Chemicals

Tetrodotoxin
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...

(TTX), used by puffer fish and some types of newts for defense. It blocks sodium channels.
Saxitoxin
Saxitoxin
Saxitoxin is a neurotoxin naturally produced by certain species of marine dinoflagellates and cyanobacteria Saxitoxin (STX) is a neurotoxin naturally produced by certain species of marine dinoflagellates (Alexandrium sp., Gymnodinium sp., Pyrodinium sp.) and cyanobacteria Saxitoxin (STX) is a...

, is produced by a dinoflagellate
Dinoflagellate
The dinoflagellates are a large group of flagellate protists. Most are marine plankton, but they are common in fresh water habitats as well. Their populations are distributed depending on temperature, salinity, or depth...

also known as "red tide
Red tide
Red tide is a common name for a phenomenon also known as an algal bloom , an event in which estuarine, marine, or fresh water algae accumulate rapidly in the water column and results in discoloration of the surface water. It is usually found in coastal areas...

". It blocks voltage dependent sodium channels.
Conotoxin
Conotoxin
A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of...

, is used by cone snails to hunt prey.
Lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...

and Novocaine belong to a class of local anesthetics which block sodium ion channels.
Dendrotoxin
Dendrotoxin
Dendrotoxins are a class of neurotoxins produced by mamba snakes that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions...

is produced by mamba
Mamba
Mambas, of the genus Dendroaspis , are a group of highly venomous, fast-moving land-dwelling snakes of Africa. They belong to the family of Elapidae which includes cobras, coral snakes, taipans, brown snakes, tiger snakes, death adders, kraits and, debatably, sea snakes...

snakes, and blocks potassium channels.
Iberiotoxin
Iberiotoxin
Iberiotoxin is an ion channel toxin purified from the Eastern Indian red scorpion Buthus tamulus.Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels.- Chemistry :...

is produced by the Buthus tamulus and blocks potassium channels.
Heteropodatoxin
Heteropodatoxin
Heteropodatoxins are peptide toxins from the venom of the giant crab spider Heteropoda venatoria, which block Kv4.2 voltage-gated potassium channels.- Source :Heteropodatoxins are purified from the venom of the giant crab spider, Heteropoda venatoria ....

is produced by Heteropoda venatoria and blocks potassium channels.

Genetic

Shaker gene
Shaker gene
The shaker gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster. Under ether anesthesia, the fly’s legs will shake ; even when the fly is unanaesthetized, it will exhibit aberrant movements...

mutations cause a defect in the voltage gated ion channels, slowing down the repolarization of the cell.
Equine hyperkalaemic periodic paralysis as well as Human hyperkalaemic periodic paralysis (HyperPP) are caused by a defect in voltage dependent sodium channels.
Paramyotonia congenita
Paramyotonia congenita
Paramyotonia Congenita , also known as Paramyotonia congenita of von Eulenburg or Eulenburg disease, is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia...

(PC) and potassium aggravated myotonias (PAM)
Generalized epilepsy with febrile seizures plus
Generalized epilepsy with febrile seizures plus
Generalized epilepsy with febrile seizures plus is a syndromic autosomal dominant disorder where afflicted individuals can exhibit numerous epilepsy phenotypes. GEFS+ can persist beyond early childhood...

(GEFS+)
Episodic Ataxia
Episodic ataxia
Episodic ataxia is an autosomal dominant disorder characterized by sporadic bouts of ataxia with or without myokymia . There are seven types recognised but the majority are due to two recognized entities. Ataxia can be provoked by stress, startle, or heavy exertion such as exercise. Symptoms can...

(EA), characterized by sporadic bouts of severe discoordination with or without myokymia, and can be provoked by stress, startle, or heavy exertion such as exercise.
Familial hemiplegic migraine
Familial hemiplegic migraine
Familial hemiplegic migraine is an autosomal dominant classical migraine subtype that typically includes hemiparesis during the aura phase. It can be accompanied by other symptoms, such as ataxia, coma and epileptic seizures...

(FHM)
Spinocerebellar ataxia type 13
Long QT syndrome
Long QT syndrome
The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...

is a ventricular
Ventricle (heart)
In the heart, a ventricle is one of two large chambers that collect and expel blood received from an atrium towards the peripheral beds within the body and lungs. The Atria primes the Pump...

arrhythmia syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

caused by mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

s in one or more of presently ten different gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s, most of which are potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...

s and all of which affect cardiac repolarization
Repolarization
In neuroscience, repolarization refers to the change in membrane potential that returns the membrane potential to a negative value after the depolarization phase of an action potential has just previously changed the membrane potential to a positive value. Repolarization results from the movement...

.
Brugada syndrome
Brugada syndrome
The Brugada syndrome is a genetic disease that is characterised by abnormal electrocardiogram findings and an increased risk of sudden cardiac death. It is named by the Spanish cardiologists Pedro Brugada and Josep Brugada...

is another ventricular arrhythmia caused by voltage-gated sodium channel gene mutations.
Cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

is caused by mutations in the CFTR gene, which is a chloride channel.
Mucolipidosis type IV
Mucolipidosis type IV
Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation...

is caused by mutations in the gene encoding the TRPML1 channel

History

The fundamental properties of currents mediated by ion channels were analyzed by the British biophysicist

Biophysics

Biophysics is an interdisciplinary science that uses the methods of physical science to study biological systems. Studies included under the branches of biophysics span all levels of biological organization, from the molecular scale to whole organisms and ecosystems...

s Alan Hodgkin and Andrew Huxley

Andrew Huxley

Sir Andrew Fielding Huxley, OM, FRS is an English physiologist and biophysicist, who won the 1963 Nobel Prize in Physiology or Medicine for his experimental and mathematical work with Sir Alan Lloyd Hodgkin on the basis of nerve action potentials, the electrical impulses that enable the activity...

as part of their Nobel Prize

Nobel Prize in Physiology or Medicine

The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

-winning research on the action potential

Action potential

In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

, published in 1952. They built on the work of other physiologists, such as Cole and Baker's research into voltage-gated membrane pores from 1941. The existence of ion channels was confirmed in the 1970s by Bernard Katz

Bernard Katz

Sir Bernard Katz, FRS was a German-born biophysicist, noted for his work on nerve biochemistry. He shared the Nobel Prize in physiology or medicine in 1970 with Julius Axelrod and Ulf von Euler...

and Ricardo Miledi

Ricardo Miledi

Ricardo Miledi is a Mexican neuroscientist who won the Royal Medal in 1998.In 1999 was awarded with the . In 2010 won the outstanding contributions to the field.He is a professor at the University of California, Irvine....

using noise analysis. It was then shown more directly with an electrical recording technique

Electrophysiology

known as the "patch clamp

Patch clamp

", which led to a Nobel Prize to Erwin Neher

Erwin Neher

Erwin Neher is a German biophysicist.Erwin Neher studied physics at the Technical University of Munich from 1963 to 1966. In 1966, He was awarded a Fulbright Scholarship to study in the US...

and Bert Sakmann

Bert Sakmann

-External links:*...

, the technique's inventors. Hundreds if not thousands of researchers continue to pursue a more detailed understanding of how these proteins work. In recent years the development of automated patch clamp devices helped to increase significantly the throughput in ion channel screening.

The Nobel Prize in Chemistry for 2003 was awarded to two American scientists: Roderick MacKinnon

Roderick MacKinnon

for his studies on the physico-chemical properties of ion channel structure and function, including x-ray crystallographic

X-ray crystallography

X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...

structure

Protein structure

Proteins are an important class of biological macromolecules present in all organisms. Proteins are polymers of amino acids. Classified by their physical size, proteins are nanoparticles . Each protein polymer – also known as a polypeptide – consists of a sequence formed from 20 possible L-α-amino...

studies, and Peter Agre

Peter Agre

Peter Agre is an American medical doctor, professor, and molecular biologist who was awarded the 2003 Nobel Prize in Chemistry for his discovery of aquaporins. Aquaporins are water-channel proteins that move water molecules through the cell membrane...

for his similar work on aquaporin

Aquaporin

Aquaporins are proteins embedded in the cell membrane that regulate the flow of water.Aquaporins are integral membrane proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells....

The ion channel in fine art

Roderick MacKinnon

commissioned Birth of an Idea, a 5 feet (1.5 m) tall sculpture based on the KcsA potassium channel. The artwork contains a wire object representing the channel's interior with a blown glass object representing the main cavity of the channel structure.

External links

AurSCOPE Ion Channels Database

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

Basic features

Biological role

Diversity

By gating

Voltage-gated

Ligand-gated

Other gating

By ions

Other classifications

Detailed structure

Diseases of ion channels

History

The ion channel in fine art

See also

Further reading

External links