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Tamapin
Tamapin is a toxin from the Indian Red Scorpion (''Hottentotta tamulus''), which is a selective and potent blocker of SK2 channels. Etymology Tamapin is named after the scorpion from which it was isolated. Sources Tamapin has been isolated from ''hottentotta tamulus'', the Indian red scorpion. Chemical structure and methods of isolation Tamapin belongs to short-chain scorpion toxin subfamily 5, together with PO5 and Scyllatoxin. Its sequence similarity to other toxins that can compete with the binding site of apamin is much lower. It is 31 amino acids long and its weight is 3458 Daltons. Its amino acid sequence is AFCNLRRCELSCRSLGLLGKCIGEECKCVPY, with disulfide bonds between Cys3-Cys21, Cys8-Cys26, and Cys12-Cys28 (chemical formula C146H234N42O42S6). Tamapin has been isolated via detection of the apamin-competing fraction of the venom from the scorpion via a Sephadex G-50 size exclusion chromatography, followed by high performance liquid chromatography (HPLC). An isoform ...
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Hottentotta Tamulus
''Hottentotta tamulus'', the Indian red scorpion, also known as the eastern Indian scorpion, is a species of scorpion of the family Buthidae. It occurs in most of India, eastern Pakistan and the eastern lowlands of Nepal, and recently from Sri Lanka. Taxonomy This species was named ''Scorpio tamulus'' by J.C. Fabricius in 1798. The species name was apparently derived from the occurrence in the state/province of the Tamil people of southeastern India. It was later often referred to the genera '' Buthus'' or ''Mesobuthus'', although it was already correctly placed in ''Hottentotta'' by A. A. Birula in 1914, a referral that was confirmed again by F. Kovařík in 2007. Nevertheless, the binomen ''Mesobuthus tamulus'' is traditionally widespread in the popular and scientific literature. R.I. Pocock (1900) distinguished five subspecies according to coloration and distribution, but these are color-morphs (individuals with varying color) rather than subspecies. Description Total b ...
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Hottentotta Tamulus
''Hottentotta tamulus'', the Indian red scorpion, also known as the eastern Indian scorpion, is a species of scorpion of the family Buthidae. It occurs in most of India, eastern Pakistan and the eastern lowlands of Nepal, and recently from Sri Lanka. Taxonomy This species was named ''Scorpio tamulus'' by J.C. Fabricius in 1798. The species name was apparently derived from the occurrence in the state/province of the Tamil people of southeastern India. It was later often referred to the genera '' Buthus'' or ''Mesobuthus'', although it was already correctly placed in ''Hottentotta'' by A. A. Birula in 1914, a referral that was confirmed again by F. Kovařík in 2007. Nevertheless, the binomen ''Mesobuthus tamulus'' is traditionally widespread in the popular and scientific literature. R.I. Pocock (1900) distinguished five subspecies according to coloration and distribution, but these are color-morphs (individuals with varying color) rather than subspecies. Description Total b ...
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SK Channel
SK channels (small conductance calcium-activated potassium channels) are a subfamily of calcium-activated potassium channels. They are so called because of their small single channel conductance in the order of 10 pS. SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium through N-type calcium channels. Their activation limits the firing frequency of action potentials and is important for regulating afterhyperpolarization in the neurons of the central nervous system as well as many other types of electrically excitable cells. This is accomplished through the hyperpolarizing leak of positively charged potassium ions along their concentration gradient into the extracellular space. This hyperpolarization causes the membrane potential to become more negative. SK channels are thought to be involved in synaptic plasticity and therefore play important roles in l ...
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Synaptosomes
A synaptosome is an isolated synaptic terminal from a neuron. Synaptosomes are obtained by mild Homogenization (biology), homogenization of nervous tissue under isotonic conditions and subsequent fractionation using differential and density gradient centrifugation. Liquid shear detaches the nerve terminals from the axon and the plasma membrane surrounding the nerve terminal particle reseals. Synaptosomes are osmotically sensitive, contain numerous Small clear-core vesicle, small clear synaptic vesicles, sometimes Large dense-core vesicle, larger dense-core vesicles and frequently one or more small mitochondria. They carry the morphological features and most of the chemical properties of the original nerve terminal. Synaptosomes isolated from mammalian brain often retain a piece of the attached postsynaptic membrane, facing the active zone. Synaptosomes were first isolated in an attempt to identify the subcellular compartment corresponding to the fraction of so-called bound acetylcho ...
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Tamulotoxin
Tamulotoxin (or Tamulus toxin, Tamulustoxin, in short form: TmTx) is a venomous neurotoxin from the Indian Red Scorpion (''Hottentotta tamulus'', ''Mesobuthus tamulus'' or ''Buthus tamulus''). Chemistry Structure The toxin has been classified as a short-chain scorpion toxin. It consists of 36 amino acids and is referred to as TmTx1. A peptide consisting of 35 amino acids has also been identified, referred to as TmTx2. It possesses three intra-molecular disulphide bonds (S-S), leading to a highly stabilized conformation. It also has six cysteine residues which is a characteristic shared by many short-chain scorpion toxins. Family TmTx belongs to the short scorpion toxin superfamily and the potassium channel inhibitor family. Adhering to the nomenclature of Tytgat et al., potassium toxins can be divided into four subgroups: alpha, beta, gamma and kappa. It belongs to the group of alpha potassium toxins (α-KTx: alpha toxin affecting potassium channels). This group contains shor ...
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Iberiotoxin
Iberiotoxin (IbTX) is an ion channel toxin purified from the Eastern Indian red scorpion ''Hottentotta tamulus''. Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels. Chemistry Iberiotoxin is a 37-amino acid peptide. The formula is C179H274N50O55S7. It is also known as "Potassium channel toxin alpha-KTx 1.3" or IbTx. The complete amino acid sequence has been defined and it displays 68% sequence homology with charybdotoxin. Target and mode of action Iberiotoxin binds to the outer face of the large-conductance calcium-activated potassium channels (maxiK or BK channels) with high affinity (Kd ~1 nM). It selectively inhibits the current by decreasing both the probability of opening and the open time of the channel. Toxicity The venom produces mainly cardiopulmonary abnormalities like circulatory derangements, myocarditis and changes in cardiac sarcolemmal ATPase and by these abnormalities it can finally cause death. In rur ...
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Potassium Channel Blockers
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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Venom
Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a stinger, in a process called envenomation. Venom is often distinguished from poison, which is a toxin that is passively delivered by being ingested, inhaled, or absorbed through the skin, and toxungen, which is actively transferred to the external surface of another animal via a physical delivery mechanism. Venom has evolved in terrestrial and marine environments and in a wide variety of animals: both predators and prey, and both vertebrates and invertebrates. Venoms kill through the action of at least four major classes of toxin, namely necrotoxins and cytotoxins, which kill cells; neurotoxins, which affect nervous systems; myotoxins, which damage muscles; and haemotoxins, which disrupt blood clotting. Venomous animals cause tens of thousa ...
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Apamin
Apamin is an 18 amino acid globular peptide neurotoxin found in apitoxin ( bee venom). Dry bee venom consists of 2–3% of apamin. Apamin selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system. Toxicity is caused by only a few amino acids, in particular cysteine1, lysine4, arginine13, arginine14 and histidine18. These amino acids are involved in the binding of apamin to the Ca2+-activated K+ channel. Due to its specificity for SK channels, apamin is used as a drug in biomedical research to study the electrical properties of SK channels and their role in the afterhyperpolarizations occurring immediately following an action potential. Origin The first symptoms of apitoxin (bee venom), that are now thought to be caused by apamin, were described back in 1936 by Hahn and Leditschke. Apamin was first isolated by Habermann in 1965 from ''Apis mellifera'', the Western honey bee. Apamin was named after this bee. Bee venom contains many ...
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Toxin
A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849–1919) and is derived from the word toxic. Toxins can be small molecules, peptides, or proteins that are capable of causing disease on contact with or absorption by body tissues interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their toxicity, ranging from usually minor (such as a bee sting) to potentially fatal even at extremely low doses (such as botulinum toxin). Toxins are largely secondary metabolites, which are organic compounds that are not directly involved in an organism's growth, development, or reproduction, instead often aiding it in matters of defense. Terminology Toxins are often distinguished from other chemical agents strictly based on their biological origin. Le ...
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High Performance Liquid Chromatography
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material. Each component in the sample interacts slightly differently with the adsorbent material, causing different flow rates for the different components and leading to the separation of the components as they flow out of the column. HPLC has been used for manufacturing (''e.g.'', during the production process of pharmaceutical and biological products), legal (''e.g.'', detecting performance enhancement drugs in urine), research (''e.g.'', separating the components of a complex biological sample, or of similar synthetic chemicals from each other), and medical (''e.g.'', detecting vitamin D levels in blood serum) purposes. Chrom ...
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KCNN2
Potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2, also known as KCNN2, is a protein which in humans is encoded by the KCNN2 gene. KCNN2 is an ion channel protein also known as KCa2.2. Function Action potentials in vertebrate neurons are followed by an afterhyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the firing pattern of the neuron. Each component of the AHP is kinetically distinct and is mediated by different calcium-activated potassium channels. The KCa2.2 protein is activated before membrane hyperpolarization and is thought to regulate neuronal excitability by contributing to the slow component of synaptic AHP. KCa2.2 is an integral membrane protein that forms a voltage-independent calcium-activated channel with three other calmodulin-binding subunits. This protein is a member of the calcium-activated potassium channel family. Two transcript variants encoding different isoforms ha ...
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