Tetrodotoxin
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Tetrodotoxin
Tetrodotoxin (TTX) is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered in these fish and found in several other animals (e.g., in blue-ringed octopuses, rough-skinned newts, and moon snails), it is actually produced by certain infecting or symbiotic bacteria like ''Pseudoalteromonas'', ''Pseudomonas'', and ''Vibrio'' as well as other species found in animals. Tetrodotoxin is a sodium channel blocker. It inhibits the firing of action potentials in neurons by binding to the voltage-gated sodium channels in nerve cell membranes and blocking the passage of sodium ions (responsible for the rising phase of an action potential) into the neuron. This prevents the nervous system from carrying messages and thus muscles from contracting in response to nervous stimulation. Its mechanism of action, selective blocking o ...
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Blue-ringed Octopus
Blue-ringed octopuses, comprising the genus ''Hapalochlaena'', are four highly venomous species of octopus that are found in tide pools and coral reefs in the Pacific and Indian oceans, from Japan to Australia. They can be identified by their yellowish skin and characteristic blue and black rings that change color dramatically when the animal is threatened. They eat small crustaceans, including crabs, hermit crabs, shrimp, and other small sea animals. They are one of the world's most venomous marine animals. Despite their small size——and relatively docile nature, they are very dangerous to humans if provoked when handled because their venom contains the powerful neurotoxin tetrodotoxin. The species tend to have a lifespan of approximately two to three years. This may vary depending on factors such as nutrition, temperature and the intensity of light within its habitat. Classification The genus was described by British zoologist Guy Coburn Robson in 1929. There are four co ...
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Neurotoxin
Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nervous tissue.Olney 2002 The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol (drinking alcohol), glutamate,Choi 1987 nitric oxide, botulinum toxin (e.g. Botox), tetanus toxin,Simpson 1986 and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations. Neurotoxins inhibit neuron control over ion concentrations across the cell membrane, or com ...
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Action Potential
An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and in some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells. In neurons, action potentials play a central role in cell-cell communication by providing for—or with regard to saltatory conduction, assisting—the propagation of signals along the neuron's axon toward synaptic boutons situated at the ends of an axon; these signals can then connect with other neurons at synapses, or to motor cells or glands. In other types of cells, their main function is to activate intracellular processes. In muscle cells, for example, an action potential is the first step in the chain of events l ...
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John Wilson Moore
John Wilson Moore (November 1, 1920 – March 30, 2019) was an American biophysicist who pioneered the emergent power of computers, beginning in the 1950s, to reveal how signals are generated, integrated, and then travel in neurons. He is well known for his discovery (with Toshio Narahashi), that the puffer fish toxin tetrodotoxin causes death by blocking the sodium ion channels that are responsible for nerve activity. Moore was emeritus professor of Neurobiology at Duke University Medical School where he had been a member of the faculty since 1961. Moore's NEURON simulator software, begun with and now carried forward by Michael Hines, is used worldwide. Moore received the Cole Award of the Biophysical Society in 1981. Early life and education Moore was born in November 1920 in Winston-Salem, North Carolina, where his father was superintendent of the Winston-Salem public schools. He studied physics at Davidson College and entered a graduate program in physics at the University o ...
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Sodium Channel Blocker
Sodium channel blockers are drugs which impair the conduction of sodium ions (Na+) through sodium channels. Extracellular The following naturally-produced substances block sodium channels by binding to and occluding the extracellular pore opening of the channel: * Alkaloids: ** Saxitoxin (STX) ** Neosaxitoxin (NSTX) ** Tetrodotoxin (TTX) Intracellular Drugs which block sodium channels by blocking from the intracellular side of the channel include: * Local anesthetics: ''lidocaine'' * Class I antiarrhythmic agents * Various anticonvulsants: ''phenytoin, oxcarbazepine (derivative of carbamazepine)'' Unknown mechanism * Calcium has been shown to block sodium channels which explains the effects of hypercalcemia and hypocalcemia. * Lamotrigine is known to block sodium channels but it is not known whether it is extracellular or intracellular. * Cannabidiol (CBD) has been shown to cause inhibitory effects on sodium currents. This voltage-dependent inhibition is non-selective in nature ...
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Toshio Narahashi
Toshio Narahashi (January 30, 1927 – April 21, 2013) was an internationally known pharmacologist. He was the John Evans Professor of Pharmacology and former chair of the Department of Pharmacology at Northwestern University Feinberg School of Medicine, where he served on the faculty from 1977 to 2013. Prior, he was vice chairman of the Department of Physiology and Pharmacology at Duke University, where he served on the faculty from 1962 to 1977. He is considered by many to be the "founding father of neurotoxicology" and is credited with discovering how tetrodotoxin, the poison in puffer fish, immobilizes parts of the nervous system. Born in Tokyo, Japan, Narahashi received an undergraduate degree in agriculture from the University of Tokyo in 1948. According to the Chicago Tribune, "He began his career studying insecticides in an entomology lab. His findings in the lab helped form the basis of 26 published papers and a doctorate in neurotoxicology that he would earn in 1960 f ...
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Pufferfish
Tetraodontidae is a family of primarily marine and estuarine fish of the order Tetraodontiformes. The family includes many familiar species variously called pufferfish, puffers, balloonfish, blowfish, blowies, bubblefish, globefish, swellfish, toadfish, toadies, toadle, honey toads, Haaris Anwar fish, sugar toads, and sea squab. They are morphologically similar to the closely related porcupinefish, which have large external spines (unlike the thinner, hidden spines of the Tetraodontidae, which are only visible when the fish have puffed up). The scientific name refers to the four large teeth, fused into an upper and lower plate, which are used for crushing the hard shells of crustaceans and mollusks, their natural prey. The majority of pufferfish species are toxic and some are among the most poisonous vertebrates in the world. In certain species, the internal organs, such as the liver, and sometimes the skin, contain tetrodotoxin, and are highly toxic to most animals when ea ...
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Voltage-gated Sodium Channels
Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change ("voltage-gated", "voltage-sensitive", or "voltage-dependent" sodium channel; also called "VGSCs" or "Nav channel") or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. These channels go through three different states called resting, active and inactive states. Even though the resting and inactive states would not allow the ions to flow through the channels the difference exists with respect to their structural conformation. Selectivity Sodium channels are highly selective for the transport of ions across cell membr ...
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Neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. Non-animals like plants and fungi do not have nerve cells. Neurons are typically classified into three types based on their function. Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells of the sensory organs, and they send signals to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. When multiple neurons are connected together, they form what is called a neural circuit. A typical neuron consists of a cell body (soma), dendrites, and a single axon. The soma is a compact structure, and the axon and dend ...
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Cell Membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to ions a ...
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Zwitterion
In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively- and negatively-charged functional groups. : With amino acids, for example, in solution a chemical equilibrium will be established between the "parent" molecule and the zwitterion. Betaines are zwitterions that cannot isomerize to an all-neutral form, such as when the positive charge is located on a quaternary ammonium group. Similarly, a molecule containing a phosphonium group and a carboxylate group cannot isomerize. Amino acids The equilibrium is established in two stages. In the first stage, a proton is transferred from the carboxyl group to a water molecule: :H2N(R)CO2H + H2O H2N(R)CO2- + H3O+ In the second stage, a proton is transferred from the hydronium ion to the amine group: :H2N(R)CO2- + H3O+ H3N+ (R)CO2- + H2O Overall, the reaction is an isomerization reaction :H2N(R)CO2H H3N+ (R)CO2- The ratio of the concentrations of the two spec ...
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Vibrio
''Vibrio'' is a genus of Gram-negative bacteria, possessing a curved-rod (comma) shape, several species of which can cause foodborne infection, usually associated with eating undercooked seafood. Being highly salt tolerant and unable to survive in fresh water, ''Vibrio'' spp. are commonly found in various salt water environments. ''Vibrio'' spp. are facultative anaerobes that test positive for oxidase and do not form spores. All members of the genus are motile. They are able to have polar or lateral flagellum with or without sheaths. ''Vibrio'' species typically possess two chromosomes, which is unusual for bacteria. Each chromosome has a distinct and independent origin of replication, and are conserved together over time in the genus. Recent phylogenies have been constructed based on a suite of genes (multilocus sequence analysis). O. F. Müller (1773, 1786) described eight species of the genus ''Vibrio'' (included in Infusoria), three of which were spirilliforms. Some of the o ...
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