Ligand-gated Ion Channel
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Ligand-gated Ion Channel
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. The neurotransmitter then binds to receptors located on the postsynaptic neuron. If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a depolarization, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain wh ...
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Inotropic
An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction. The term ''inotropic state'' is most commonly used in reference to various drugs that affect the strength of contraction of heart muscle. However, it can also refer to pathological conditions. For example, enlarged heart muscle can increase inotropic state, whereas dead heart muscle can decrease it. Medical uses Both positive and negative inotropes are used in the management of various cardiovascular conditions. The choice of agent depends largely on specific pharmacological effects of individual agents with respect to the condition. One of the most important factors affecting inotropic state is the level of calcium in the cytoplasm of the muscle cell. Positive inotropes usually increase this level, while negative inotropes decrease it. However, not al ...
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Synapse
In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from one neuron to another. Neurons are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the ''presynaptic'' neuron) comes into close apposition with the membrane of the target (''postsynaptic'') cell. Both the presynaptic and postsynaptic sites contain extensive arrays of molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an axon and the postsynaptic part is located on a dendrite or soma. Astrocytes also exchange information with the synaptic neurons, responding to synaptic activity and, in turn, regulating neurotransmission. Syna ...
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Alpha Helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earlier along the protein sequence. The alpha helix is also called a classic Pauling–Corey–Branson α-helix. The name 3.613-helix is also used for this type of helix, denoting the average number of residues per helical turn, with 13 atoms being involved in the ring formed by the hydrogen bond. Among types of local structure in proteins, the α-helix is the most extreme and the most predictable from sequence, as well as the most prevalent. Discovery In the early 1930s, William Astbury showed that there were drastic changes in the X-ray fiber diffraction of moist wool or hair fibers upon significant stretching. The data suggested that the unstretched fibers had a coiled molecular structure with a characteristic repeat of ≈. Astb ...
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Cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometimes the symbol Cyz is used. The deprotonated form can generally be described by the symbol Cym as well. The thiol is susceptible to oxidation to give the disulfide derivative cystine, which serves an important structural role in many proteins. In this case, the symbol Cyx is sometimes used. When used as a food additive, it has the E number E920. Cysteine is encoded by the codons UGU and UGC. The sulfur-containing amino acids cysteine and methionine are more easily oxidized than the other amino acids. Structure Like other amino acids (not as a residue of a protein), cysteine exists as a zwitterion. Cysteine has chirality in the older / notation based on homology to - and -glyceraldehyde. In the newer ''R''/''S'' system of designating chi ...
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Cys-loop Receptors
The Cys-loop ligand-gated ion channel superfamily is composed of nicotinic acetylcholine, GABAA, GABAA-ρ, glycine, 5-HT3, and zinc-activated (ZAC) receptors. These receptors are composed of five protein subunits which form a pentameric arrangement around a central pore. There are usually 2 alpha subunits and 3 other beta, gamma, or delta subunits (some consist of 5 alpha subunits). The name of the family refers to a characteristic loop formed by 13 highly conserved amino acids between two cysteine (Cys) residues, which form a disulfide bond near the N-terminal extracellular domain. Cys-loop receptors are known only in eukaryotes, but are part of a larger family of pentameric ligand-gated ion channels. Only the Cys-loop clade includes the pair of bridging cysteine residues. The larger superfamily includes bacterial (e.g. GLIC) as well as non-Cys-loop eukaryotic receptors, and is referred to as "pentameric ligand-gated ion channels", or "Pro-loop receptors". All subunits consis ...
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P2X Purinoreceptor
The ATP-gated P2X receptor cation channel familyTC# 1.A.7, or simply P2X receptor family, consists of cation-permeable ligand-gated ion channels that open in response to the binding of extracellular adenosine 5'-triphosphate ( ATP). They belong to a larger family of receptors known as the ENaC/P2X superfamily. ENaC and P2X receptors have similar 3-D structures and are homologous. P2X receptors are present in a diverse array of organisms including humans, mouse, rat, rabbit, chicken, zebrafish, bullfrog, fluke, and amoeba. Physiological roles P2X receptors are involved in a variety of physiological processes, including: * Modulation of cardiac rhythm and contractility * Modulation of vascular tone * Mediation of nociception, especially chronic pain * Contraction of the vas deferens during ejaculation * Contraction of the urinary bladder during micturition * Platelet aggregation * Macrophage activation * Apoptosis * Neuronal- glial integration Tissue distribution P2X receptors ...
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Glutamate-gated Ion Channel Family
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in synaptic plasticity, which is important for learning and memory. iGluRs have been divided into four subtypes on the basis of their ligand binding properties (pharmacology) and sequence similarity: AMPA receptors, kainate receptors, NMDA receptors and delta receptors (see below). AMPA receptors are the main charge carriers during basal transmission, permitting influx of sodium ions to depolarise the postsynaptic membrane. NMDA receptors are blocked by magnesium ions and therefore only permit ion flux following prior depolarisation. This enables them to act as coincidence detectors for synaptic plasticity. Calcium influx through NMDA receptors leads to persistent modifications in the strength of synaptic transmission. iGluRs are tetramer ...
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Cys-loop Receptor
The Cys-loop ligand-gated ion channel superfamily is composed of nicotinic acetylcholine, GABAA, GABAA-ρ, glycine, 5-HT3, and zinc-activated (ZAC) receptors. These receptors are composed of five protein subunits which form a pentameric arrangement around a central pore. There are usually 2 alpha subunits and 3 other beta, gamma, or delta subunits (some consist of 5 alpha subunits). The name of the family refers to a characteristic loop formed by 13 highly conserved amino acids between two cysteine (Cys) residues, which form a disulfide bond near the N-terminal extracellular domain. Cys-loop receptors are known only in eukaryotes, but are part of a larger family of pentameric ligand-gated ion channels. Only the Cys-loop clade includes the pair of bridging cysteine residues. The larger superfamily includes bacterial (e.g. GLIC) as well as non-Cys-loop eukaryotic receptors, and is referred to as "pentameric ligand-gated ion channels", or "Pro-loop receptors". All subunits consi ...
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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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Channel Blockers
A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel. Ion channels permit the selective passage of ions through cell membranes by utilizing proteins that function as pores, which allow for the passage of electrical charge in and out of the cell. These ion channels are most often gated, meaning they require a specific stimulus to cause the channel to open and close. These ion channel types regulate the flow of charged ions across the membrane and therefore mediate membrane potential of the cell. Molecules that act as channel blockers are important in the field of pharmacology, as a large portion of drug des ...
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Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure. Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association or docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of lig ...
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