Potassium channel
Encyclopedia
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
, potassium channels are the most widely distributed type of ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
and are found in virtually all living organisms. They form 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...
-selective pores that span cell 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. Furthermore potassium channels are found in most 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....
types and control a wide variety of cell functions.
Function
In excitable cells such as neuronNeuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, they shape 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 and set the resting membrane potential
Resting potential
The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....
.
By contributing to the regulation of the action potential
Cardiac action potential
In electrocardiography, the cardiac action potential is a specialized action potential in the heart, necessary for the electrical conduction system of the heart....
duration in cardiac muscle
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...
, malfunction of potassium channels may cause life-threatening arrhythmias. Potassium channels may also be involved in maintaining vascular tone.
They also regulate cellular processes such as the secretion of hormones (e.g., 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 from beta-cells
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
in the pancreas
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...
) so their malfunction can lead to diseases (such as diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
).
Types
There are four major classes of potassium channels:- Calcium-activated potassium channelCalcium-activated potassium channelCalcium-activated potassium channels are divided into BK channels, IK channels, and SK channels based on their conductance ....
- open in response to the presence of calciumCalciumCalcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ions or other signalling molecules. - Inwardly rectifying potassium channelInward-rectifier potassium ion channelInwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
- passes current (positive charge) more easily in the inward direction (into the cell). - Tandem pore domain potassium channelTandem pore domain potassium channelThe 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...
- are constitutively open or possess high basal activation, such as the "resting potassium channels" or "leak channels" that set the negative membrane potential of neurons. When open, they allow potassium ions to cross the membrane at a rate that is nearly as fast as their diffusionDiffusionMolecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...
through bulk waterWaterWater is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
. - Voltage-gated potassium channelVoltage-gated potassium channelVoltage-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....
- are voltage-gated ion channelVoltage-gated ion channelVoltage-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 that open or close in response to changes in the transmembraneMembrane potentialMembrane 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...
voltageVoltageVoltage, 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...
.
The following table contains a comparison of the major classes of potassium channels with representative examples (for a complete list of channels within each class, see the respective class pages).
| Class | Subclasses | Function | Blockers | Activators |
|---|---|---|---|---|
| Calcium-activated Calcium-activated potassium channel Calcium-activated potassium channels are divided into BK channels, IK channels, and SK channels based on their conductance .... 6T 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... & 1P |
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Charybdotoxin Charybdotoxin is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system.-Chemical properties:... , 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 :... Apamin Apamin is an 18 amino acid peptide neurotoxin found in apitoxin . It selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system and smooth muscle... |
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| Inwardly rectifying 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... 2T 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... & 1P |
ROMK ROMK is an acronym for the Renal Outer Medullary Potassium channel. This is an ATP-dependent potassium channel that transports potassium out of cells. It plays an important role in potassium recycling in the thick ascending limb and potassium secretion in the cortical collecting duct of the... (Kir1.1) |
Nephron The renal tubule is the portion of the nephron containing the tubular fluid filtered through the glomerulus. After passing through the renal tubule, the filtrate continues to the collecting duct system, which is not part of the nephron.... s |
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G protein-coupled inwardly-rectifying potassium channel The G protein-coupled inwardly-rectifying potassium channels are a family of inward-rectifier potassium ion channels which are activated via a signal transduction cascade starting with ligand-stimulated G protein-coupled receptors . GPCRs in turn release activated G-protein βγ- subunits from... (Kir3.x) |
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Ifenprodil Ifenprodil is a selective inhibitor of the NMDA receptor. Its effect is specific to receptors composed of the NR1 and NR2B subunits.... |
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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... is high to promote 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.... secretion |
Glibenclamide Glibenclamide , also known as glyburide , is an antidiabetic drug in a class of medications known as sulfonylureas, closely related to sulfa drugs... Tolbutamide Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug sold under the brand name Orinase. This drug may be used in the management of type II diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by the pancreas... |
Diazoxide Diazoxide is a potassium channel activator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions... Pinacidil Pinacidil is a cyanoguanidine drug that opens ATP-sensitive potassium channels producing peripheral vasodilatation of arterioles. It reduces blood pressure and peripheral resistance and produces fluid retention.... |
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| Tandem pore domain 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... 4T 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... & 2P |
KCNK1 Potassium channel subfamily K member 1 is a protein that in humans is encoded by the KCNK1 gene.... , TWIK-2 KCNK6 Potassium channel subfamily K member 6 is a protein that in humans is encoded by the KCNK6 gene.... , KCNK7 KCNK7 Potassium channel, subfamily K, member 7, also known as KCNK7 or K2P7.1 is a protein which in humans is encoded by the KCNK7 gene. K2P7.1 is a potassium channel containing two pore-forming P domains... ) KCNK2 Potassium channel subfamily K member 2 is a protein that in humans is encoded by the KCNK2 gene.- External links :... , TREK-2 KCNK10 Potassium channel, subfamily K, member 10, also known as KCNK10 is a human gene. The protein encoded by this gene, K2P10.1, is a potassium channel containing two pore-forming P domains.... , TRAAK KCNK4 Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene.... ) KCNK3 Potassium channel subfamily K member 3 is a protein that in humans is encoded by the KCNK3 gene.-Interactions:KCNK3 has been shown to interact with YWHAB and S100A10.- External links :... , TASK-3 KCNK9 Potassium channel subfamily K member 9 is a protein that in humans is encoded by the KCNK9 gene.This gene encodes K2P9.1, one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. This open channel is highly expressed in the cerebellum... , TASK-5 KCNK15 Potassium channel subfamily K member 15 is a protein that in humans is encoded by the KCNK15 gene.... ) KCNK5 Potassium channel subfamily K member 5 is a protein that in humans is encoded by the KCNK5 gene.... , TALK-1 KCNK16 Potassium channel subfamily K member 16 is a protein that in humans is encoded by the KCNK16 gene. The protein encoded by this gene, K2P16.1, is a potassium channel containing two pore-forming P domains.... , TALK-2 KCNK17 Potassium channel subfamily K member 17 is a protein that in humans is encoded by the KCNK17 gene.... ) KCNK13 Potassium channel, subfamily K, member 13, also known as KCNK13 is a human gene. The protein encoded by this gene, K2P13.1 is a potassium channel containing two pore-forming P domains.... , THIK-2 KCNK12 Potassium channel, subfamily K, member 12, also known as KCNK12 is a human gene. The protein encoded by this gene, K2P12.1, is a potassium channel containing two pore-forming P domains.... ) KCNK18 Potassium channel subfamily K member 18 , also known as TWIK-related spinal cord potassium channel or K2P18.1 is a protein that in humans is encoded by the KCNK18 gene. K2P18.1 is a potassium channel containing two pore-forming P domains.A flaw in this gene could help trigger migraine headaches... |
Resting potential The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential.... |
Bupivacaine Bupivacaine is a local anaesthetic drug belonging to the amino amide group. AstraZeneca commonly markets it under various trade names, including Marcain, Marcaine, Sensorcaine and Vivacaine.-Indications:... Quinidine Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:... |
Halothane Halothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and... |
| Voltage-gated 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.... 6T 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... & 1P |
HERG hERG is a gene that codes for a protein known as Kv11.1 potassium ion channel... (Kv11.1) KvLQT1 Kv7.1 is a potassium channel protein coded for by the gene KCNQ1. Kv7.1 is present in the cell membranes of cardiac muscle tissue and in inner ear neurons among other tissues... (Kv7.1) |
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... 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... Dysrhythmia Dysrhythmia is an American instrumental progressive metal band formed in Philadelphia, Pennsylvania in 1998. The band's music combines avant-garde elements of progressive rock and jazz with heavy metal... ) |
Tetraethylammonium Tetraethylammonium is a quaternary ammonium cation consisting of four ethyl groups attached to a central nitrogen atom. Like other members of its class, it can be used to alter a compound's solubility by displacing hard acids with this comparatively softer acid... 4-Aminopyridine 4-Aminopyridine is an organic compound with the chemical formula C5H4N–NH2. The molecule is one of the three isomeric amines of pyridine... 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... s (some types) |
Retigabine Retigabine or ezogabine , codenamed D-23129, is an anticonvulsant used as a treatment for partial epilepsies. The drug was developed by Valeant Pharmaceuticals and GlaxoSmithKline... (Kv7) |
Structure
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...
s associate to form a fourfold symmetric
Symmetry
Symmetry generally conveys two primary meanings. The first is an imprecise sense of harmonious or aesthetically pleasing proportionality and balance; such that it reflects beauty or perfection...
(C4) complex arranged around a central ion conducting pore (i.e., a homotetramer). Alternatively four related but not identical protein subunits may associate to form heterotetrameric complexes with pseudo C4 symmetry. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selective permeability.
There are over 80 mammalian genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
that encode potassium channel 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...
s. However potassium channels found in bacteria are amongst the most studied of ion channels, in terms of their molecular structure. Using X-ray crystallography
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...
, profound insights have been gained into how potassium ions pass through these channels and why (smaller) 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...
ions do not. The 2003 Nobel Prize for Chemistry was awarded to Rod 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....
for his pioneering work in this area.
Selectivity filter
The carbonyl oxygens are strongly electro-negative and cation-attractive. The filter can accommodate potassium ions at 4 sites usually labelled S1 to S4 starting at the extracellular side. In addition, one ion can bind in the cavity at a site called SC or one or more ions at the extracellular side at more or less well-defined sites called S0 or Sext. Several different occupancies of these sites are possible. Since the X-ray structures are averages over many molecules, it is, however, not possible to deduce the actual occupancies directly from such a structure. In general, there is some disadvantage due to electrostatic repulsion to have two neighbouring sites occupied by ions. The mechanism for ion translocation in KcsA has been studied extensively by simulation techniques. A complete map of the free energies of the 24=16 states (characterised by the occupancy of the S1, S2, S3, and S4 sites) has been calculated with molecular dynamics simulations, resulting in the prediction of an ion conduction mechanism in which the two doubly occupied states (S1, S3) and (S2, S4) play an essential role. The two extracellular states, Sext and S0, were found in a better resolved structure of KcsA at high potassium concentration. In free energy calculations, the entire ionic pathway from the cavity through the four filter sites out to S0 and Sext was covered in MD simulations. The amino acids sequence of the selectivity filter of potassium ion channels is conserved, with the exception that an isoleucine residue in eukaryotic potassium ion channels often is substituted with a valine residue in prokaryotic channels.
Hydrophobic region
This region is used to neutralize the environment around the potassium ion so that it is not attracted to any charges. In turn, it speeds up the reaction.Central cavity
A central pore, 10 Å wide, is located near the center of the transmembrane channel, where the energy barrier is highest for the transversing ion due to the hydrophobity of the channel wall. The water-filled cavity and the polar C-terminus of the pore helices ease the energetic barrier for the ion. Repulsion by preceding multiple potassium ions is thought to aid the throughput of the ions.The presence of the cavity can be understood intuitively as one of the channel's mechanisms for overcoming the dielectric barrier, or repulsion by the low-dielectric membrane, by keeping the K+ ion in a watery, high-dielectric environment.
Blockers
Potassium channel blockerPotassium channel blocker
Potassium channel blockers are agents which interfere with conduction through potassium channels.-Arrhythmia:Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic agents.-Mechanism:...
s, such as 4-aminopyridine
4-Aminopyridine
4-Aminopyridine is an organic compound with the chemical formula C5H4N–NH2. The molecule is one of the three isomeric amines of pyridine...
and 3,4-diaminopyridine
3,4-Diaminopyridine
3,4-Diaminopyridine is an organic compound with the formula C5H3N2. It is formally derived from pyridine by substitution of the 3 and 4 positions with an amino group....
, have been investigated for the treatment of conditions such as multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
.
Muscarinic potassium channel
See also G protein-coupled inwardly-rectifying potassium channel
G protein-coupled inwardly-rectifying potassium channel
The G protein-coupled inwardly-rectifying potassium channels are a family of inward-rectifier potassium ion channels which are activated via a signal transduction cascade starting with ligand-stimulated G protein-coupled receptors . GPCRs in turn release activated G-protein βγ- subunits from...
Some types of potassium channels are activated by muscarinic receptors and these are called muscarinic potassium channels (IKACh). These channels are a heterotetramer composed of two GIRK1
KCNJ3
Potassium inwardly-rectifying channel, subfamily J, member 3, also known as KCNJ3 or Kir3.1, is a human gene.-See also:* G protein-coupled inwardly-rectifying potassium channel* Inward-rectifier potassium ion channel- External links :...
and two GIRK4
KCNJ5
G protein-activated inward rectifier potassium channel 4 is a protein that in humans is encoded by the KCNJ5 gene and is a type of G protein-gated ion channel.-See also:* G protein-coupled inwardly-rectifying potassium channel...
subunits. Examples are potassium channels in the heart, which, when activated by parasympathetic signals through M2 muscarinic receptors, causes an outward current of potassium, which slows down the heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
.
Potassium channels in fine art
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....
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.