SK3
Encyclopedia
SK3 is a small-conductance calcium-activated potassium channel
partly responsible for the calcium
-dependent after hyperpolarisation current (IAHP). It belongs to a family of channels known as small-conductance potassium channel
s, which consists of three members – SK1, SK2 and SK3 (KCNN1, 2 and 3 respectively), which share a 60-70% sequence identity. These channels have acquired a number of alternative names, however a NC-IUPHAR has recently achieved consensus on the best names, KCa2.1 (SK1), KCa2.2 (SK2) and KCa2.3 (SK3). Small conductance channels are responsible for the medium and possibly the slow components of the IAHP.
. The gene for KCa2.3, KCNN3, is located on chromosome
1q21.
, placenta
, adipose tissue
, liver
, prostate
and skin
. KCa2.3 is most abundant in regions of the brain
, but has also been found to be expressed in significant levels in many other peripheral tissues, particularly those rich in smooth muscle
, including the rectum
, corpus cavernosum
, colon
, small intestine
and myometirum.
The expression
level of KCNN3 is dependent on hormonal
regulation, particularly by the sex hormone estrogen
. Estrogen not only enhances transcription
of the KCNN3 gene, but also affects the activity of KCa2.3 channels on the cell membrane
. In GABA
ergic POA neurons, estrogen enhanced the ability of α1 adrenergic receptor
s to inhibit KCa2.3 activity, increasing cell excitability. Links between hormonal regulation of sex organ
function and KCa2.3 expression have been established. The expression of KCa2.3 in the corpus cavernosum in patients undergoing estrogen treatment as part of gender reassignment surgery was found to be increased up to 5-fold. The influence of estrogen on KCa2.3 has also been established in the hypothalamus
, uterine
and skeletal muscle
.
relaxation. The expression level of KCa2.3 channels in the endothelium
influences arterial
tone by setting arterial smooth muscle membrane potential
. The sustained activity of KCa2.3 channels induces a sustained hyperpolarisation
of the endothelial cell membrane potential, which is then carried to nearby smooth muscle through gap junctions. Blocking the KCa2.3 channel or suppressing KCa2.3 expression causes a greatly increased tone in resistance arteries, producing an increase in peripheral resistance and blood pressure
.
s in KCa2.3 are suspected to be a possible underlying cause for several neurological disorder
s, including schizophrenia
, bipolar disorder
, Alzheimer’s disease, anorexia nervosa
and ataxia
as well as myotonic muscular dystrophy.
Calcium-activated potassium channel
Calcium-activated potassium channels are divided into BK channels, IK channels, and SK channels based on their conductance ....
partly responsible for the 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...
-dependent after hyperpolarisation current (IAHP). It belongs to a family of channels known as small-conductance potassium channel
SK channel
SK channels are a subfamily of Ca2+-activated K+ channels. They are so called because of their small single channel conductance, ~10 pS. SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated by an increase in the concentration of...
s, which consists of three members – SK1, SK2 and SK3 (KCNN1, 2 and 3 respectively), which share a 60-70% sequence identity. These channels have acquired a number of alternative names, however a NC-IUPHAR has recently achieved consensus on the best names, KCa2.1 (SK1), KCa2.2 (SK2) and KCa2.3 (SK3). Small conductance channels are responsible for the medium and possibly the slow components of the IAHP.
Structure
KCa2.3 contains 6 transmembrane domains, a pore-forming region, and intracellular N- and C- termini and is readily blocked by apaminApamin
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...
. The gene for KCa2.3, KCNN3, is located on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
1q21.
Expression
KCa2.3 is found in almost every tissue in the human body, with exceptions being the pancreasPancreas
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...
, placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
, adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
and skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
. KCa2.3 is most abundant in regions of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, but has also been found to be expressed in significant levels in many other peripheral tissues, particularly those rich in 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...
, including the rectum
Rectum
The rectum is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long...
, corpus cavernosum
Corpus cavernosum
Corpus cavernosum may refer to:* corpus cavernosum clitoridis* corpus cavernosum penis* "corpus cavernosum urethrae" was used for corpus spongiosum in older texts* corpus cavernosum conchae...
, colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
, small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
and myometirum.
The expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
level of KCNN3 is dependent on hormonal
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
regulation, particularly by the sex hormone estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
. Estrogen not only enhances transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of the KCNN3 gene, but also affects the activity of KCa2.3 channels on the 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...
. In GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
ergic POA neurons, estrogen enhanced the ability of α1 adrenergic receptor
Alpha-1 adrenergic receptor
The alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...
s to inhibit KCa2.3 activity, increasing cell excitability. Links between hormonal regulation of sex organ
Sex organ
A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive...
function and KCa2.3 expression have been established. The expression of KCa2.3 in the corpus cavernosum in patients undergoing estrogen treatment as part of gender reassignment surgery was found to be increased up to 5-fold. The influence of estrogen on KCa2.3 has also been established in the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, uterine
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
and skeletal muscle
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...
.
Physiology
KCa2.3 channels play a major role in human physiology, particularly in smooth muscleSmooth 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...
relaxation. The expression level of KCa2.3 channels in the endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
influences arterial
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
tone by setting arterial smooth muscle 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...
. The sustained activity of KCa2.3 channels induces a sustained hyperpolarisation
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...
of the endothelial cell membrane potential, which is then carried to nearby smooth muscle through gap junctions. Blocking the KCa2.3 channel or suppressing KCa2.3 expression causes a greatly increased tone in resistance arteries, producing an increase in peripheral resistance and blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
.
Pathology
MutationMutation
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 KCa2.3 are suspected to be a possible underlying cause for several neurological disorder
Neurological disorder
A neurological disorder is a disorder of the body's nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord, or in the nerves leading to or from them, can result in symptoms such as paralysis, muscle weakness, poor coordination, loss of sensation, seizures,...
s, including schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
, Alzheimer’s disease, anorexia nervosa
Anorexia nervosa
Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...
and ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
as well as myotonic muscular dystrophy.