Potassium Channels
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Potassium Channels
Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions. Function Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly (up to the diffusion rate of K+ ions in bulk water) and selectively (excluding, most notably, sodium despite the sub-angstrom difference in ionic radius). Biologically, these channels act to set or reset the resting potential in many cells. In excitable cells, such as neurons, the delayed counterflow of potassium ions shapes the action potential. By contributing to the regulation of the cardiac action potential duration in cardiac muscle, malfunction of potassium channels may cause life-threatening arrhythmias. Potassium channels may also be involved in maintaining vascular tone. They also regulate ce ...
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Insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially o ...
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Potassium Channel Blocker
Potassium channel blockers are agents which interfere with conduction through potassium channels. Medical uses Arrhythmia Potassium channel blockers used in the treatment of cardiac arrhythmia are classified as class III antiarrhythmic agents. Mechanism Class III agents predominantly block the potassium channels, thereby prolonging repolarization. More specifically, their primary effect is on IKr. Since these agents do not affect the sodium channel, conduction velocity is not decreased. The prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias. (The re-entrant rhythm is less likely to interact with tissue that has become refractory). Examples and uses *Amiodarone is indicated for the treatment of refractory VT or VF, particularly in the setting of acute ischemia. Amiodarone is also safe to use in individuals with cardiomyopathy and atrial fibrillation, to main ...
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Voltage
Voltage, also known as electric pressure, electric tension, or (electric) potential difference, is the difference in electric potential between two points. In a static electric field, it corresponds to the work needed per unit of charge to move a test charge between the two points. In the International System of Units, the derived unit for voltage is named ''volt''. The voltage between points can be caused by the build-up of electric charge (e.g., a capacitor), and from an electromotive force (e.g., electromagnetic induction in generator, inductors, and transformers). On a macroscopic scale, a potential difference can be caused by electrochemical processes (e.g., cells and batteries), the pressure-induced piezoelectric effect, and the thermoelectric effect. A voltmeter can be used to measure the voltage between two points in a system. Often a common reference potential such as the ground of the system is used as one of the points. A voltage can represent either a source ...
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Membrane Potential
Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges to move from the internal to exterior cellular environments and vice versa, as long as there is no acquisition of kinetic energy or the production of radiation. The concentration gradients of the charges directly determine this energy requirement. For the exterior of the cell, typical values of membrane potential, normally given in units of milli volts and denoted as mV, range from –80 mV to –40 mV. All animal cells are surrounded by a membrane composed of a lipid bilayer with proteins embedded in it. The membrane serves as both an insulator and a diffusion barrier to the movement of ions. Transmembrane proteins, also known as ion transporter or ion pump proteins, actively push ions across the membrane and establish concentration gradi ...
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Voltage-gated Ion Channel
Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between ...
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Voltage-gated Potassium Channel
Voltage-gated potassium channels (VGKCs) 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. Classification Alpha subunits Alpha subunits form the actual conductance pore. Based on sequence homology of the hydrophobic transmembrane cores, the alpha subunits of voltage-gated potassium channels are grouped into 12 classes. These are labeled Kvα1-12. The following is a list of the 40 known human voltage-gated potassium channel alpha subunits grouped first according to function and then subgrouped according to the Kv sequence homology classification scheme: Delayed rectifier slowly inactivating or non-inactivating *Kvα1.x - Shaker-related: Kv1.1 (KCNA1), Kv1.2 (KCNA2), Kv1.3 (KCNA3), Kv1.5 (KCNA5), Kv1.6 (KCNA6), Kv1.7 ( KCNA7), Kv1.8 (KCNA10) *Kvα2.x - Shab-related: Kv2.1 (KCNB1), Kv2.2 (KCNB2) *Kvα3.x - ...
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Tandem Pore Domain Potassium Channel
The two-pore-domain or tandem pore domain potassium channels are a family of 15 members that form what is known as leak channels which possess Goldman-Hodgkin-Katz (open) rectification. These channels are regulated by several mechanisms including signaling lipids, oxygen tension, pH, mechanical stretch, and G-proteins . Their name is derived from the fact that the α subunits consist of four transmembrane segments, and each pair of transmembrane segments contains a pore loop between the two transmembrane segments. Thus, each subunit has two pore loops. As such, they structurally correspond to two inward-rectifier α subunits and thus form dimers in the membrane (whereas inward-rectifier α subunits form tetramers). Each single channel does ''not'' have two pores; the name of the channel comes from the fact that ''each subunit'' has two P (pore) domains in its primary sequence. To quote Rang and Dale (2015), "The nomenclature is misleading, especially when they are incorrectly ...
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Inward-rectifier Potassium Ion Channel
Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinositol 4,5-bisphosphate ( PIP2). The malfunction of the channels has been implicated in several diseases. IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport potassium (K+), with a greater tendency for K+ uptake than K+ export. The process of inward-rectification was discovered by Denis Noble in cardiac muscle cells in 1960s and by Richard Adrian and Alan Hodgkin in 1970 in skeletal muscle cells. Overview of inward rectification A channel that is "inwardly-rectifying" is one that passes current (positive cha ...
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Calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to its heavier homologues strontium and barium. It is the fifth most abundant element in Earth's crust, and the third most abundant metal, after iron and aluminium. The most common calcium compound on Earth is calcium carbonate, found in limestone and the fossilised remnants of early sea life; gypsum, anhydrite, fluorite, and apatite are also sources of calcium. The name derives from Latin ''calx'' "lime", which was obtained from heating limestone. Some calcium compounds were known to the ancients, though their chemistry was unknown until the seventeenth century. Pure calcium was isolated in 1808 via electrolysis of its oxide by Humphry Davy, who named the element. Calcium compounds are widely used in many industries: in foods and pharma ...
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Calcium-activated Potassium Channel
Calcium-activated potassium channels are potassium channels gated by calcium, or that are structurally or phylogenetically related to calcium gated channels. They were first discovered in 1958 by Gardos who saw that calcium levels inside of a cell could affect the permeability of potassium through that cell membrane. Then in 1970, Meech was the first to observe that intracellular calcium could trigger potassium currents. In humans they are divided into three subtypes: BK channel, large conductance or BK channels, which have very high conductance which range from 100 to 300 pS, intermediate conductance or IK channels, with intermediate conductance ranging from 25 to 100 pS, and small conductance or SK channels with small conductances from 2-25 pS. This family of ion channels is, for the most part, activated by intracellular Ca2+ and contains 8 members in the human genome. However, some of these channels (the KCa4 and KCa5 channels) are responsive instead to other intracellular ligan ...
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Dendrotoxin
Dendrotoxins are a class of presynaptic neurotoxins produced by mamba snakes (''Dendroaspis'') that block particular subtypes of voltage-gated potassium channels in neurons, thereby enhancing the release of acetylcholine at neuromuscular junctions. Because of their high potency and selectivity for potassium channels, dendrotoxins have proven to be extremely useful as pharmacological tools for studying the structure and function of these ion channel proteins. Functional effects in the nervous system Dendrotoxins have been shown to block particular subtypes of voltage-gated potassium (K+) channels in neuronal tissue. In the nervous system, voltage-gated K+ channels control the excitability of nerves and muscles by controlling the resting membrane potential and by repolarizing the membrane during action potentials. Dendrotoxin has been shown to bind the nodes of Ranvier of motor neurons and to block the activity of these potassium channels. In this way, dendrotoxins prolong the ...
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