BK channel
Encyclopedia
BK channels also called Maxi-K or slo1, are ion channel
s characterized by their large conductance of potassium
ions (K+) through cell membrane
s. These channels are activated (opened) by changes in membrane electrical potential
and/or by increases in concentration of intracellular
calcium
ion (Ca2+). Opening of BK channels allows K+ to passively flow through the channel, down the electrochemical gradient
. Under typical physiological conditions, this results in an efflux of K+ from the cell, which leads to cell membrane hyperpolarization
(a decrease in the electrical potential across the cell membrane) and a decrease in cell excitability (a decrease in the probability that the cell will transmit an action potential
).
BK channels are essential for the regulation of several key physiological processes including smooth muscle
tone
and neuronal excitability. They control the contraction of smooth muscle and are involved with the electrical tuning
of hair cell
s in the cochlea
. BK channels also contribute to the behavioral effects of ethanol
in the worm C. elegans
under high concentrations (> 100 mM, or approximately 0.50% BAC). It remains to be determined if BK channels contribute to intoxication in humans.
of the channel-forming alpha subunit is the product of the KCNMA1
gene. Modulatory beta subunits (encoded by KCNMB1
, KCNMB2
, KCNMB3
, or KCNMB4
) can associate with the tetrametic channel.
BK channels are a prime example of modular protein evolution. Each BK channel alpha subunit consists of (from N- to C-terminal):
Available X-ray structures: - Crystal Structure of the Human BK Gating Apparatus - Structure of the Intracellular Gating Ring from the Human High-conductance Ca2+ gated K+ Channel (BK Channel)
failed to improve clinical outcome in stroke patients compared to placebo
. BK channels have also been found to be activated by exogenous pollutants and endogenous gazotransmitters carbon monoxide and hydrogen sulphide.
BK channels are blocked by tetraethylammonium (TEA), paxilline
and iberiotoxin
.
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...
s characterized by their large conductance of 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...
ions (K+) through 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. These channels are activated (opened) by changes in membrane electrical 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...
and/or by increases in concentration of intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
calcium
Calcium
Calcium 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...
ion (Ca2+). Opening of BK channels allows K+ to passively flow through the channel, down the 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...
. Under typical physiological conditions, this results in an efflux of K+ from the cell, which leads to cell membrane 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...
(a decrease in the electrical potential across the cell membrane) and a decrease in cell excitability (a decrease in the probability that the cell will transmit an 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...
).
BK channels are essential for the regulation of several key physiological processes including 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...
tone
Muscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
and neuronal excitability. They control the contraction of smooth muscle and are involved with the electrical tuning
Electrical tuning
Electrical tuning is a mechanism by which vertebrates such as frogs and reptiles, which lack a long cochlea, discriminate sound. Mammals have long cochleae, and are able to distinguish different sounds by mechanisms such as mechanical tuning, in which the stiffness and length of hair cells’...
of hair cell
Hair cell
Hair cells are the sensory receptors of both the auditory system and the vestibular system in all vertebrates. In mammals, the auditory hair cells are located within the organ of Corti on a thin basilar membrane in the cochlea of the inner ear...
s in the cochlea
Cochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
. BK channels also contribute to the behavioral effects of ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
in the worm C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
under high concentrations (> 100 mM, or approximately 0.50% BAC). It remains to be determined if BK channels contribute to intoxication in humans.
Structure
As with other potassium channels, BK channels have a tetrameric structure. Each monomerMonomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
of the channel-forming alpha subunit is the product of the KCNMA1
KCNMA1
Calcium-activated potassium channel subunit alpha-1 also known as potassium large conductance calcium-activated channel, subfamily M, alpha member 1 is a voltage gated ion channel encoded by the KCNMA1 gene.- Function :...
gene. Modulatory beta subunits (encoded by KCNMB1
KCNMB1
Calcium-activated potassium channel subunit beta-1 is a protein that in humans is encoded by the KCNMB1 gene.-Further reading:...
, KCNMB2
KCNMB2
Calcium-activated potassium channel subunit beta-2 is a protein that in humans is encoded by the KCNMB2 gene.MaxiK channels are large conductance, voltage and calcium-sensitive potassium channels which are fundamental to the control of smooth muscle tone and neuronal excitability...
, KCNMB3
KCNMB3
Calcium-activated potassium channel subunit beta-3 is a protein that in humans is encoded by the KCNMB3 gene.-Further reading:...
, or KCNMB4
KCNMB4
Calcium-activated potassium channel subunit beta-4 is a protein that in humans is encoded by the KCNMB4 gene.-Further reading:...
) can associate with the tetrametic channel.
BK channels are a prime example of modular protein evolution. Each BK channel alpha subunit consists of (from N- to C-terminal):
- A unique transmembrane domain (S0) that precedes the 6 transmembrane domains (S1-S6) conserved in all voltage-dependent K+ channels.
- A voltage sensing domain (S1-S4).
- A K+ channel pore domain (S5, selectivity filter, and S6).
- A cytoplasmic C-terminal domain (CTD) consisting of a pair of RCK domains that assemble into an octameric gating ring on the intracellular side of the tetrameric channel. The CTD contains four primary binding sites for Ca2+, called "calcium bowls", encoded within the second RCK domain of each monomer.
Available X-ray structures: - Crystal Structure of the Human BK Gating Apparatus - Structure of the Intracellular Gating Ring from the Human High-conductance Ca2+ gated K+ Channel (BK Channel)
Pharmacology
BK channels are pharmacological targets for the treatment of stroke. Various pharmaceutical companies developed synthetic molecules activating these channels in order to prevent excessive neurotoxic calcium entry in neurons. But BMS-204352 (MaxiPost) a molecule developed by Bristol-Myers SquibbBristol-Myers Squibb
Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
failed to improve clinical outcome in stroke patients compared to placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
. BK channels have also been found to be activated by exogenous pollutants and endogenous gazotransmitters carbon monoxide and hydrogen sulphide.
BK channels are blocked by tetraethylammonium (TEA), paxilline
Paxilline
Paxilline is a potassium channel blocker. Paxilline is a toxic, tremorgenic indole alkaloid produced by Penicillium paxilli.Disambiguation:Paxilline, a mycotoxin of penicillium origin, should not be confused with...
and 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 :...
.