Sodium channels (also known as "voltage-gated sodium channels") are integral membrane proteins that are localized in and conduct sodium ions (Na⁺) through a cell's plasma membrane. Many of the ionotropic receptors are also able to conduct sodium ions and are discussed elsewhere. In excitable cells such as neurons and myocytes, sodium channels are responsible for the rising phase of action potentials. An Integral Membrane Protein (IMP) is a protein molecule (or assembly of proteins) that is permanently attached to the biological membrane. ... General Name, Symbol, Number sodium, Na, 11 Chemical series alkali metals Group, Period, Block 1, 3, s Appearance silvery white Atomic mass 22. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hook from Micrographia which is the origin of the word cell. Cells in culture, stained for keratin (red) and DNA (green). ... Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... Wikipedia does not yet have an article with this exact name. ... Wikipedia does not yet have an article with this exact name. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... It has been suggested that this article or section be merged into Muscular system. ... Schematic of an electrophysiological recording of an action potential showing the various phases which occur as the wave passes a point on a cell membrane. ...

Structure

Diagram of a voltage-sensitive sodium channel α-subunit. G - glycosylation, P - phosphorylation, S - ion selectivity, I - inactivation, positive (+) charges in S4 are important for transmembrane voltage sensing^[1].

Sodium channels can often be isolated from cells as a complex of two types of protein subunits, α and β. An α subunit forms the core of the channel. When the α subunit protein is expressed by a cell, it is able to form channels which conduct Na⁺ in a voltage-gated way, even if β subunits are not expressed. When β subunits assemble with α subunits the resulting complex can display altered voltage dependence and cellular localization. Image File history File links Download high-resolution version (1125x469, 34 KB) I (John Schmidt) made this diagram for Wikipedia based on Overview of the voltage-gated sodium channel family. ... Image File history File links Download high-resolution version (1125x469, 34 KB) I (John Schmidt) made this diagram for Wikipedia based on Overview of the voltage-gated sodium channel family. ... Glycosylation is the process or result of addition of saccharides to proteins and lipids. ... Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule. ...

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. Conservation is a high degree of similarity in the primary or higher structure of homologous proteins amongst various phyla. ...

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 milliseconds 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 Na⁺ channel inactivation cause muscle stiffness because of the introduction of a window current. One millisecond is one-thousandth of a second. ...

The temporal behaviour of sodium channels can be described by a Markovian scheme or by the Hodgkin-Huxley-type formalism. In the former scheme, each channel occupies a distinct state with differential equations 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. State transitions in a hidden Markov model (example) x — hidden states y — observable outputs a — transition probabilities b — output probabilities A hidden Markov model (HMM) is a statistical model where the system being modeled is assumed to be a Markov process with unknown parameters, and the challenge is to determine... The Hodgkin-Huxley Model is a set of non-linear ordinary differential equations, named after Alan Lloyd Hodgkin and Andrew Huxley, that approximates the electrical characteristics of excitable cells such as neurons and cardiac myocytes. ... In physics, the term state is used in several related senses, each of which expresses something about the way a physical system is. ... An illustration of a differential equation. ...

Impermeability to other ions

The pore of sodium channels contains a selectivity filter made of negatively charged amino acid 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. A pore, in general, is some form of opening, usually very small. ... The general structure of an α-amino acid molecule, with the amine group on the left and the carboxyl group on the right. ... The chloride ion is formed when the element chlorine picks up one electron to form an anion (negatively-charged ion) Cl−. The salts of hydrochloric acid HCl contain chloride ions and are also called chlorides. ... A nanometre (American spelling: nanometer) is 1. ... Water is an odourless substance that is essential to all known forms of life and is known as the universal solvent. ... In chemistry, a molecule is an aggregate of two or more atoms in a definite arrangement held together by chemical bonds [1] [2] [3] [4] [5]. Chemical substances are not infinitely divisible into smaller fractions of the same substance: a molecule is generally considered the smallest particle of a pure... Glutamate is the anion of glutamic acid. ...

Diversity

Figure 1. Likely evolutionary relationship of the nine known human sodium channels.

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 maintain by the IUPHAR.^[2] The proteins of these channels are named Na_v1.1 through Na_v1.9. The gene names are referred to as SCN1A through SCN11A (the SCN6/7A gene is part of the Na_x 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.

It has been suggested that this article or section be merged with GEFS. (Discuss) Generalized epilepsy with febrile seizures or GEFS refers to a genetic disorder of the neuron. ... A top-down view of skeletal muscle Skeletal muscle is a type of striated muscle, attached to the skeleton. ... Hyperkalemic periodic paralysis (HYPP), also known as Impressive Syndrome, is an inherited autosomal dominant disorder which affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood of horses. ... Paramyotonia congenita is a rare congenital neuromuscular disorder which is characterized by a condition in which the muscles do not relax after contracting (myotonia). ... SCN5A is a sodium ion channel associated with long QT syndrome type 3 (LQT3), Brugada syndrome, and idiopathic ventricular fibrillation. ... The long QT syndrome (LQTS) is a heart disease in which there is an abnormally long delay between the electrical excitation (or depolarization) and relaxation (repolarization) of the ventricles of the heart. ... The Brugada syndrome is a genetic disease that is manifest by abnormal electrocardiogram (ECG) findings and an increased risk of sudden cardiac death. ... Ventricular fibrillation (V-fib or VF) is a cardiac condition which consists of a lack of coordination of the contraction of the muscle tissue of the large chambers of the heart that eventually leads to the heart stopping altogether. ... This is a dorsal root ganglion (DRG) from a chicken embryo (around stage of day 7) after incubation overnight in NGF growth medium stained with anti-neurofilament antibody. ... This is a dorsal root ganglion (DRG) from a chicken embryo (around stage of day 7) after incubation overnight in NGF growth medium stained with anti-neurofilament antibody. ... Schwann cells are a variety of neuroglia that wrap around axons in the peripheral nervous system, forming the myelin sheath. ... Erythromelalgia, also known as Mitchells disease (after Silas Weir Mitchell) and red neuralgia, is a rare disorder in which blood vessels, usually in the extremities and especially in the feet, are blocked and inflamed, causing a painful burning and throbbing sensation and red skin. ...

Role in action potential

Voltage-gated ion channel sodium channels play a significant role in action potentials. If enough channels open when there is a change in the cell's membrane potential, a large number of Na⁺ ions will rush 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. A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. ... This article or section is in need of attention from an expert on the subject. ... In cellular biology, an electrochemical gradient refers to the electrical and chemical properties across a membrane. ... In biology, depolarization is the event a cell undergoes when its membrane potential grows more positive with respect to the extracellular solution. ... Positive feedback is a type of feedback. ...

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. In cell biology, potassium channels are the most common type of ion channel. ... A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. ...

References

• Eric R. Kandel, Schwartz JH, Jessell TM. Principles of Neural Science, 4th ed., pp.154-169. McGraw-Hill, New York (2000). ISBN 0-8385-7701-6
• Bertil Hille Ion channels of excitable membranes, 3rd ed., Sinauer Associates, Sunderland, MA (2001). ISBN 0-87893-321-2
• Catterall, WA, Goldin, AL, and Waxman, SG. (2005), International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacol. Rev. 57, 397-409. Entrez PubMed 16382098

Eric Richard Kandel (born November 7, 1929) is a psychiatrist, a neuroscientist and professor of biochemistry and biophysics at Columbia University. ... Principles of Nerual Science cover First published in 1981, Principles of Neural Science is a neuroscience textbook edited by Eric R. Kandel, James Schwartz, and Thomas Jessell. ... Dr. Bertil Hille is an American biologist. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ...

See also

• Ion channels
• Calcium channels
• Potassium channels
• Resting ion channels
• Epithelial sodium channel

Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ... Ion channels are present in the membranes that surround all biological cells. ... In cell biology, potassium channels are the most common type of ion channel. ... Resting channels are ion channels in the plasma membrane of a cell that remain open at all times. ... Sodium channels (also known as voltage-gated sodium channels) are integral membrane proteins that are localized in and conduct sodium ions (Na+) through a cells plasma membrane. ...

External links

• MeSH Sodium+Channels