Sodium ion channel
Encyclopedia
Sodium channels are integral membrane protein
s that form ion channels, conducting sodium ions (Na+
) through a cell's
plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change (voltage-gated sodium channels) or binding of a substance (a ligand
) to the channel (ligand-gated sodium channels).
In excitable cells such as neuron
s, myocytes
, and certain types of glia, sodium channels are responsible for the rising phase of action potentials.
The α-subunit has four repeat domains, labeled I through IV, each containing six membrane-spanning regions, labeled S1 through S6. The highly conserved S4 region acts as the channel's voltage sensor. The voltage sensitivity of this channel is due to positive amino acids located at every third position. When stimulated by a change in transmembrane voltage, this region moves toward the extracellular side of the cell membrane, allowing the channel to become permeable to ions. The ions are conducted through a pore, which can be broken into two regions. The more external (i.e., more extracellular) portion of the pore is formed by the "P-loops" (the region between S5 and S6) of the four domains. This region is the most narrow part of the pore and is responsible for its ion selectivity. The inner portion (i.e., more cytoplasmic) of the pore is formed by the combined S5 and S6 regions of the four domains. The region linking domains III and IV is also important for channel function. This region plugs the channel after prolonged activation, inactivating it.
s after depolarization. The inactivation is removed when the membrane potential of the cell repolarizes following the falling phase of the action potential. This allows the channels to be activated again during the next action potential. Genetic diseases that alter sodium channel inactivation can cause muscle stiffness or epileptic seizures because of the introduction of a so-called window current, during which sodium channels are tonically active, causing muscle and/or nerve cells to become over-excited.
The temporal behaviour of sodium channels can be modeled by a Markovian
scheme or by the Hodgkin-Huxley
-type formalism. In the former scheme, each channel occupies a distinct state with differential equation
s describing transitions between states; in the latter, the channels are treated as a population
that are affected by three independent gating variables. Each of these variables can attain a value between 1 (fully permeant to ions) and 0 (fully non-permeant), the product of these variables yielding the percentage of conducting channels. The Hodgkin-Huxley model can be shown to be equivalent to a Markovian model.
residues, which attract the positive Na+ ion and keep out negatively charged ions such as chloride
. The cations flow into a more constricted part of the pore that is 0.3 by 0.5 nm wide, which is just large enough to allow a single Na+ ion with a water molecule
associated to pass through. The larger K+ ion cannot fit through this area. Differently sized ions also cannot interact as well with the negatively charged glutamic acid residues that line the pore.
The family of sodium channels has nine known members, with amino acid identity >50% in the transmembrane and extracellular loop regions. A standardized nomenclature for sodium channels is currently used and is maintained by the IUPHAR.
The proteins of these channels are named Nav1.1 through Nav1.9. The gene names are referred to as SCN1A through SCN11A (the SCN6/7A gene is part of the Nax sub-family and has uncertain function). The likely evolutionary relationship between these channels, based on the similarity of their amino acid sequences, is shown in figure 1. The individual sodium channels are distinguished not only by differences in their sequence but also by their kinetics and expression profiles. Some of this data is summarized in table 1, below.
cytoskeleton
via ankyrin
and spectrin
.
Voltage-gated sodium channels also assemble with a variety of other proteins, such as FHF proteins (Fibroblast growth factor Homologous Factor), calmodulin, cytoskeleton or regulatory kinases, which form a complex with sodium channels, influencing its expression and/or function. Several beta subunits interact with one or more extracellular matrix
(ECM) molecules. Contactin, also known as F3 or F11, associates with beta 1 as shown via co-immunoprecipitation. Fibronectin
-like (FN-like) repeats of Tenascin
-C and Tenascin
-R bind with beta 2 in contrast to the Epidermal growth factor
-like (EGF-like) repeats that repel beta2. A disintegrin and metalloproteinase (ADAM) 10 sheds beta 2's ectodomain
possibly inducing neurite outgrowth. Beta 3 and beta 1 bind to neurofascin at Nodes of Ranvier in developing neurons.
instead of a change in membrane potential.
They are found e.g. in the neuromuscular junction
as nicotinic receptors, where the ligands are acetylcholine
molecules. Most channels of this type are permeable to potassium to some degree as well as to sodium.
Voltage-gated sodium channels play an important role in action potential
s. If enough channels open when there is a change in the cell's membrane potential
, a small but significant number of Na+ ions will move into the cell down their electrochemical gradient
, further depolarizing
the cell. Thus, the more Na+ channels localized in a region of a cell's membrane, the faster the action potential will propagate, and the more excitable that area of the cell will be. This is an example of a positive feedback loop. The ability of these channels to assume a closed-inactivated state causes the refractory period and is critical for the propagation of action potentials down an axon
.
Na+ channels both open and close more quickly than K+ channels
, producing an influx of positive charge (Na+) toward the beginning of the action potential
and an efflux (K+) toward the end.
Ligand-gated sodium channels, on the other hand, create the change in the membrane potential in the first place, in response to the binding of a ligand to it.
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 that form ion channels, conducting sodium ions (Na+
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...
) through a cell's
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....
plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change (voltage-gated sodium channels) or binding of a substance (a ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
) to the channel (ligand-gated sodium channels).
In excitable cells such as neuron
Neuron
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, myocytes
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
, and certain types of glia, sodium channels are responsible for the rising phase of action potentials.
Structure
Sodium channels consist of a large α subunit that associates with other proteins, such as β subunits. An α subunit forms the core of the channel and is functional on its own. When the α subunit protein is expressed by a cell, it is able to form channels that conduct Na+ in a voltage-gated way, even if β subunits or other known modulating proteins are not expressed. When accessory proteins assemble with α subunits, the resulting complex can display altered voltage dependence and cellular localization.The α-subunit has four repeat domains, labeled I through IV, each containing six membrane-spanning regions, labeled S1 through S6. The highly conserved S4 region acts as the channel's voltage sensor. The voltage sensitivity of this channel is due to positive amino acids located at every third position. When stimulated by a change in transmembrane voltage, this region moves toward the extracellular side of the cell membrane, allowing the channel to become permeable to ions. The ions are conducted through a pore, which can be broken into two regions. The more external (i.e., more extracellular) portion of the pore is formed by the "P-loops" (the region between S5 and S6) of the four domains. This region is the most narrow part of the pore and is responsible for its ion selectivity. The inner portion (i.e., more cytoplasmic) of the pore is formed by the combined S5 and S6 regions of the four domains. The region linking domains III and IV is also important for channel function. This region plugs the channel after prolonged activation, inactivating it.
Gating
Voltage-gated sodium channels have three types of states: deactivated (closed), activated (open), and inactivated (closed). Channels in the deactivated state are thought to be blocked on their intracellular side by an "activation gate", which is removed in response to stimulation that opens the channel. The ability to inactivate is thought to be due to a tethered plug (formed by domains III and IV of the alpha subunit), called an inactivation gate, that blocks the inside of the channel shortly after it has been activated. During an action potential the channel remains inactivated for a few millisecondMillisecond
A millisecond is a thousandth of a second.10 milliseconds are called a centisecond....
s after depolarization. The inactivation is removed when the membrane potential of the cell repolarizes following the falling phase of the action potential. This allows the channels to be activated again during the next action potential. Genetic diseases that alter sodium channel inactivation can cause muscle stiffness or epileptic seizures because of the introduction of a so-called window current, during which sodium channels are tonically active, causing muscle and/or nerve cells to become over-excited.
The temporal behaviour of sodium channels can be modeled by a Markovian
Hidden Markov model
A hidden Markov model is a statistical Markov model in which the system being modeled is assumed to be a Markov process with unobserved states. An HMM can be considered as the simplest dynamic Bayesian network. The mathematics behind the HMM was developed by L. E...
scheme or by the Hodgkin-Huxley
Hodgkin-Huxley model
The Hodgkin–Huxley model is a mathematical model that describes how action potentials in neurons are initiated and propagated....
-type formalism. In the former scheme, each channel occupies a distinct state with differential equation
Differential equation
A differential equation is a mathematical equation for an unknown function of one or several variables that relates the values of the function itself and its derivatives of various orders...
s describing transitions between states; in the latter, the channels are treated as a population
Statistical population
A statistical population is a set of entities concerning which statistical inferences are to be drawn, often based on a random sample taken from the population. For example, if we were interested in generalizations about crows, then we would describe the set of crows that is of interest...
that are affected by three independent gating variables. Each of these variables can attain a value between 1 (fully permeant to ions) and 0 (fully non-permeant), the product of these variables yielding the percentage of conducting channels. The Hodgkin-Huxley model can be shown to be equivalent to a Markovian model.
Impermeability to other ions
The pore of sodium channels contains a selectivity filter made of negatively charged amino acidAmino 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...
residues, which attract the positive Na+ ion and keep out negatively charged ions such as 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...
. The cations flow into a more constricted part of the pore that is 0.3 by 0.5 nm wide, which is just large enough to allow a single Na+ ion with a water molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
associated to pass through. The larger K+ ion cannot fit through this area. Differently sized ions also cannot interact as well with the negatively charged glutamic acid residues that line the pore.
Diversity
Voltage-gated sodium channels normally consist of an alpha subunit that forms the ion conduction pore and one to two beta subunits that have several functions including modulation of channel gating. Expression of the alpha subunit alone is sufficient to produce a functional channel.Alpha subunits
The proteins of these channels are named Nav1.1 through Nav1.9. The gene names are referred to as SCN1A through SCN11A (the SCN6/7A gene is part of the Nax sub-family and has uncertain function). The likely evolutionary relationship between these channels, based on the similarity of their amino acid sequences, is shown in figure 1. The individual sodium channels are distinguished not only by differences in their sequence but also by their kinetics and expression profiles. Some of this data is summarized in table 1, below.
| Protein name | Gene | Expression profile | Associated human 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... |
|---|---|---|---|
| Nav1.1 Nav1.1 Nav1.1, also known as the sodium channel, voltage-gated, type I, alpha subunit , is a protein which in humans is encoded by the SCN1A gene.-Function:... |
Central neurons Central nervous system The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish... , [peripheral neurons] and cardiac myocytes |
febrile epilepsy Epilepsy Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases... , GEFS+ 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... , Dravet syndrome (also known as severe myclonic epilepsy of infancy or SMEI), borderline SMEI (SMEB), West syndrome (also known as infantile spasms), Doose syndrome (also known as myoclonic astatic epilepsy), intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), Panayiotopoulos syndrome, familial hemiplegic migraine (FHM), familial autism, Rasmussens's encephalitis and Lennox-Gastaut syndrome |
|
| Nav1.2 Nav1.2 Navα1.2, also known as the sodium channel, voltage-gated, type II, alpha subunit is a protein that in humans is encoded by the SCN2A gene. Functional sodium channels contain an ion conductive alpha subunit and one or more regulatory beta subunits. Sodium channels which contain the Navα1.2 subunit... |
Central neurons, peripheral neurons | inherited febrile seizure Febrile seizure A febrile seizure, also known as a fever fit or febrile convulsion, is a convulsion associated with a significant rise in body temperature... s and epilepsy Epilepsy Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases... |
|
| Nav1.3 SCN3A Sodium channel, voltage-gated, type III, alpha subunit is a protein that in humans is encoded by the Nav1.3 gene.- External links :... |
Central neurons, peripheral neurons and cardiac myocytes | none known | |
| Nav1.4 | 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... |
hyperkalemic periodic paralysis Hyperkalemic periodic paralysis Hyperkalemic periodic paralysis is a genetic disorder which occurs in both humans and horses, where it is also known as Impressive Syndrome. It is an inherited autosomal dominant disorder which affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood... , 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... , and potassium-aggravated myotonia Potassium-aggravated myotonia Potassium-aggravated myotonia is a rare genetic disorder that affects skeletal muscle. Beginning in childhood or adolescence, people with this condition experience bouts of sustained muscle tensing that prevent muscles from relaxing normally... |
|
| Nav1.5 | Cardiac myocytes, uninnervated skeletal muscle, central neurons | 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... , 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... , and idiopathic ventricular fibrillation Ventricular fibrillation Ventricular fibrillation is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. Ventricular fibrillation is a medical emergency and most commonly identified arrythmia in cardiac arrest... |
|
| Nav1.6 SCN8A Sodium channel, voltage gated, type VIII, alpha subunit also known as SCN8A or Nav1.6 is a protein which in humans is encoded by the SCN8A gene... |
Central neurons, dorsal root ganglia, peripheral neurons Peripheral nervous system The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain... , heart, glia cells |
none known | |
| Nav1.7 Nav1.7 Nav1.7 is a sodium ion channel that in humans is encoded by the SCN9A gene. It is usually expressed at high levels in two types of neurons, the nociceptive neurons at dorsal root ganglion and trigeminal ganglion, and sympathetic ganglion neurons, which are part of the autonomic nervous system.-... |
Dorsal root ganglia, sympathetic neurons, Schwann cells, and neuroendocrine cells | erythromelalgia Erythromelalgia Erythromelalgia, also known as Mitchell's disease , acromelalgia, red neuralgia, or erythermalgia, is a rare neurovascular peripheral pain disorder in which blood vessels, usually in the lower extremities , are episodically blocked , then become hyperemic and inflamed... , PEPD Paroxysmal extreme pain disorder Paroxysmal extreme pain disorder , originally named familial rectal pain syndrome, is a rare disorder whose most notable features are pain in the mandibular, ocular and rectal areas as well as flushing. PEPD often first manifests at the beginning of life, perhaps even in utero, with symptoms... and channelopathy-associated insensitivity to pain Congenital insensitivity to pain Congenital insensitivity to pain , also known as congenital analgesia, is one or more rare conditions where a person cannot feel physical pain... |
|
| Nav1.8 SCN10A Sodium channel, voltage gated, type X, alpha subunit also known as SCN10A or Nav1.8 is a protein which in humans is encoded by the SCN10A gene.Nav1.8 is a sodium channel subunit.-Function:... |
Dorsal root ganglia | none known | |
| Nav1.9 Nav1.9 Sodium channel, voltage-gated, type XI, alpha subunit also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel protein which in humans is encoded by the SCN11A gene.... |
Dorsal root ganglia | none known | |
| Nax SCN7A Sodium channel protein type 7 subunit alpha is a protein that in humans is encoded by the SCN7A gene.-See also:* Sodium channelScn7a is the name of the gene that encodes to a membrane protein, in particular a Sodium Channel Nax It belongs to a family of Sodium Channel known as Voltage-Gated, but... |
heart, uterus, skeletal muscle, astrocytes, dorsal root ganglion cells | none known |
Beta subunits
Sodium channel beta subunits are type 1 transmembrane glycoproteins with an extracellular N-terminus and a cytoplasmic C-terminus. As a member of the Ig superfamily, beta subunits contain a prototypic V-set Ig loop in their extracellular domain. Interestingly, beta subunits share no homology with their counterparts of calcium and potassium channels. Instead, they are homologous to neural cell adhesion molecules (CAMs) and the large family of L1 CAMs. There are four distinct betas named in order of discovery: SCN1B, SCN2B, SCN3B, SCN4B (table 2). Beta 1 and beta 3 interact with the alpha subunit non-covalently while beta 2 and beta 4 associate with alpha via disulfide bond.Role of beta subunits as cell adhesion molecules
In addition to regulating channel gating, sodium channel beta subunits also modulate channel expression and form links to the intracelluarIntracellular
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...
cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
via ankyrin
Ankyrin
Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins...
and spectrin
Spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure...
.
Voltage-gated sodium channels also assemble with a variety of other proteins, such as FHF proteins (Fibroblast growth factor Homologous Factor), calmodulin, cytoskeleton or regulatory kinases, which form a complex with sodium channels, influencing its expression and/or function. Several beta subunits interact with one or more extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
(ECM) molecules. Contactin, also known as F3 or F11, associates with beta 1 as shown via co-immunoprecipitation. Fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
-like (FN-like) repeats of Tenascin
Tenascin
Tenascins are extracellular matrix glycoproteins. They are abundant in the extracellular matrix of developing vertebrate embryos and they reappear around healing wounds and in the stroma of some tumors.-Types:...
-C and Tenascin
Tenascin
Tenascins are extracellular matrix glycoproteins. They are abundant in the extracellular matrix of developing vertebrate embryos and they reappear around healing wounds and in the stroma of some tumors.-Types:...
-R bind with beta 2 in contrast to the Epidermal growth factor
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
-like (EGF-like) repeats that repel beta2. A disintegrin and metalloproteinase (ADAM) 10 sheds beta 2's ectodomain
Ectodomain
An ectodomain is the domain of a membrane protein that extends into the extracellular space . Ectodomains are usually the part of a protein that initiate contact with surface which leads to signal transduction. In SARS-CoV the ectodomain of the spike protein is responsible for attachment to and...
possibly inducing neurite outgrowth. Beta 3 and beta 1 bind to neurofascin at Nodes of Ranvier in developing neurons.
| Protein name | Gene link | Assembles with | Expression profile | 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... >|- | Navβ1 SCN1B Sodium channel subunit beta-1 is a protein that in humans is encoded by the SCN1B gene.-External links:*... |
Nav1.1 to Nav1.7 | Central Neurons, Peripheral Neurons, skeletal muscle, heart, glia | >- | Nav1.1, Nav1.2, Nav1.5 to Nav1.7 | Central Neurons, peripheral neurons, heart, glia | >- | Nav1.1 to Nav1.3, Nav1.5 | central neurons, adrenal gland, kidney, peripheral neurons | >- | Nav1.1, Nav1.2, Nav1.5 | heart, skeletal muscle, central and peripheral neurons |
|---|
Ligand-gated
Ligand-gated sodium channels are activated by binding of a ligandLigand (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...
instead of a change in membrane potential.
They are found e.g. in the neuromuscular junction
Neuromuscular junction
A neuromuscular junction is the synapse or junction of the axon terminal of a motor neuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract...
as nicotinic receptors, where the ligands are acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
molecules. Most channels of this type are permeable to potassium to some degree as well as to sodium.
Role in action potential
- See main article: Action potentialAction potentialIn 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...
Voltage-gated sodium channels play an important role in 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. If enough channels open when there is a change in the cell's 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...
, a small but significant number of Na+ ions will move into the cell 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...
, further depolarizing
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
the cell. Thus, the more Na+ channels localized in a region of a cell's membrane, the faster the action potential will propagate, and the more excitable that area of the cell will be. This is an example of a positive feedback loop. The ability of these channels to assume a closed-inactivated state causes the refractory period and is critical for the propagation of action potentials down an axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
.
Na+ channels both open and close more quickly than K+ channels
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...
, producing an influx of positive charge (Na+) toward the beginning of 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...
and an efflux (K+) toward the end.
Ligand-gated sodium channels, on the other hand, create the change in the membrane potential in the first place, in response to the binding of a ligand to it.
Activators
The following naturally produced substances persistently activate (open) sodium channels:- AlkaloidAlkaloidAlkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
based toxins- aconitineAconitineAconitine is a highly poisonous alkaloid derived from various aconite species.-Uses:...
- batrachotoxinBatrachotoxinBatrachotoxins are extremely potent cardiotoxic and neurotoxic steroidal alkaloids found in certain species of frogs , melyrid beetles, and birds...
- brevetoxinBrevetoxinBrevetoxin , or brevetoxins, are a suite of cyclic polyether compounds produced naturally by a species of dinoflagellate known as Karenia brevis...
- ciguatoxinCiguatoxinthumb|300px|right|Chemical structure of the ciguatoxin CTX1BThe ciguatoxins are a class of poisonous organic compounds found in some fish that causes ciguatera....
- delphinineDelphinineDelphinine is a toxic alkaloid found in plants from the Delphinium family. It is related in structure and has similar effects to aconitine, acting as an allosteric modulator of voltage gated sodium channels, and producing hypotension, bradycardia and cardiac arrythmia. These effects make it highly...
- grayanotoxinGrayanotoxinGrayanotoxins are a group of closely related toxins found in rhododendrons and other plants of the family Ericaceae. They can be found in honey made from their nectar and cause a very rare poisonous reaction called grayanotoxin poisoning, honey intoxication, or rhododendron poisoning...
- veratridineVeratridineVeratridine is a steroid-derived alkaloid from the family of Liliaceae that functions as a neurotoxin by activating sodium ion channels. It is a derivative of veracevine. It is primarily obtained from the herb Veratrum and sabadilla seeds. It binds to intramembrane receptor site 2 and increases...
- aconitine
Gating modifiers
The following toxins modify the gating of sodium channels:- PeptidePeptidePeptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
based toxins- μ-conotoxinConotoxinA 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...
- δ-atracotoxin
- Scorpion venom toxins, such as BirtoxinBirtoxinBirtoxin is a neurotoxin from the venom of the South African Spitting scorpion . By changing sodium channel activation, the toxin promotes spontaneous and repetitive firing.-Source:...
- μ-conotoxin
See also
- Ion channelIon channelIon 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 - Calcium channelCalcium channelA 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 - Potassium channelPotassium channelIn 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
- Resting ion channels
- Epithelial sodium channelEpithelial sodium channelThe 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...