Cyclic nucleotide gated cation channels. Medical search

Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.

Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.

A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.

A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), some members of this class have additional specificity for CYCLIC GMP.

Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.

Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)

A subgroup of TRP cation channels that contain 3-4 ANKYRIN REPEAT DOMAINS and a conserved C-terminal domain. Members are highly expressed in the CENTRAL NERVOUS SYSTEM. Selectivity for calcium over sodium ranges from 0.5 to 10.

A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.

Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.

The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)

The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.

Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC 3.1.4.16 and EC 3.1.4.37. EC 3.1.4.-.

An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.

A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.

Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.

A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.

A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.

Potassium channels where the flow of K+ ions into the cell is greater than the outward flow.

Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.

A class of drugs that act by selective inhibition of calcium influx through cellular membranes.

A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC 3.1.4.17), members of this class have additional specificity for CYCLIC GMP.

Positively charged atoms, radicals or group of atoms with a valence of plus 1, which travel to the cathode or negative pole during electrolysis.

Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.

N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.

The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).

The rate dynamics in chemical or physical systems.

An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.

A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.

A broad group of eukaryotic six-transmembrane cation channels that are classified by sequence homology because their functional involvement with SENSATION is varied. They have only weak voltage sensitivity and ion selectivity. They are named after a DROSOPHILA mutant that displayed transient receptor potentials in response to light. A 25-amino-acid motif containing a TRP box (EWKFAR) just C-terminal to S6 is found in TRPC, TRPV and TRPM subgroups. ANKYRIN repeats are found in TRPC, TRPV & TRPN subgroups. Some are functionally associated with TYROSINE KINASE or TYPE C PHOSPHOLIPASES.

The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.

The ability of a substrate to allow the passage of ELECTRONS.

Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.

A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.

Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.

An anthranilic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. It is used in musculoskeletal and joint disorders and administered by mouth and topically. (From Martindale, The Extra Pharmacopoeia, 30th ed, p16)

An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.

A subgroup of TRP cation channels that are widely expressed in various cell types. Defects are associated with POLYCYSTIC KIDNEY DISEASES.

A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.

An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.

A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES

Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.

Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.

Potassium channels whose activation is dependent on intracellular calcium concentrations.

A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.

A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).

Established cell cultures that have the potential to propagate indefinitely.

A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.

A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)

A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP and cyclic GMP and as an inhibitor of cat heart cyclic AMP phosphodiesterase.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.

Sodium channels found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON; the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. They are AMILORIDE-sensitive and play a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.

Voltage-gated potassium channels whose primary subunits contain six transmembrane segments and form tetramers to create a pore with a voltage sensor. They are related to their founding member, shaker protein, Drosophila.

A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.

The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.

The relationship between the dose of an administered drug and the response of the organism to the drug.

A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.

CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.

A major class of calcium activated potassium channels whose members are voltage-dependent. MaxiK channels are activated by either membrane depolarization or an increase in intracellular Ca(2+). They are key regulators of calcium and electrical signaling in a variety of tissues.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

A heterogenous group of transient or low voltage activated type CALCIUM CHANNELS. They are found in cardiac myocyte membranes, the sinoatrial node, Purkinje cells of the heart and the central nervous system.

An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.

A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.

An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous.

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.

Gadolinium. An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.

The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)

Inhibitor of phosphodiesterases.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.

The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.

A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.

A delayed rectifier subtype of shaker potassium channels that is selectively inhibited by a variety of SCORPION VENOMS.

A delayed rectifier subtype of shaker potassium channels that is the predominant VOLTAGE-GATED POTASSIUM CHANNEL of T-LYMPHOCYTES.

Elements of limited time intervals, contributing to particular results or situations.

A delayed rectifier subtype of shaker potassium channels that is commonly mutated in human episodic ATAXIA and MYOKYMIA.

A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.

A family of mechanosensitive sodium channels found primarily in NEMATODES where they play a role in CELLULAR MECHANOTRANSDUCTION. Degenerin sodium channels are structurally-related to EPITHELIAL SODIUM CHANNELS and are named after the fact that loss of their activity results in cellular degeneration.

Proteins prepared by recombinant DNA technology.

A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.

The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)

A phosphodiesterase 4 inhibitor with antidepressant properties.

Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.

Inorganic compounds derived from hydrochloric acid that contain the Cl- ion.

A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.

Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.

A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)

Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.

A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.

A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.

A member of the alkali metals. It has an atomic symbol Cs, atomic number 50, and atomic weight 132.91. Cesium has many industrial applications, including the construction of atomic clocks based on its atomic vibrational frequency.

The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.

Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.

A subfamily of shaker potassium channels that shares homology with its founding member, Shab protein, Drosophila. They regulate delayed rectifier currents in the NERVOUS SYSTEM of DROSOPHILA and in the SKELETAL MUSCLE and HEART of VERTEBRATES.

A family of proteins involved in the transport of organic cations. They play an important role in the elimination of a variety of endogenous substances, xenobiotics, and their metabolites from the body.

A voltage-gated potassium channel that is expressed primarily in the HEART.

The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.

A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).

An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.

Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.

A major class of calcium-activated potassium channels that are found primarily in excitable CELLS. They play important roles in the transmission of ACTION POTENTIALS and generate a long-lasting hyperpolarization known as the slow afterhyperpolarization.

A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)

An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.

A fast inactivating subtype of shaker potassium channels that contains two inactivation domains at its N terminus.

Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

The nonstriated involuntary muscle tissue of blood vessels.

Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.

Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.

A widely distributed purinergic P2X receptor subtype that plays a role in pain sensation. P2X4 receptors found on MICROGLIA cells may also play a role in the mediation of allodynia-related NEUROPATHIC PAIN.

Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.

Compounds based on an 8-membered heterocyclic ring including an oxygen. They can be considered medium ring ethers.

Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

A shaker subfamily that is prominently expressed in NEURONS and are necessary for high-frequency, repetitive firing of ACTION POTENTIALS.

A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.

Nucleotides in which the base moiety is substituted with one or more sulfur atoms.

Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.

A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.

A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.

Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.

The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.

Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.

Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.

Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.

A cyclic nucleotide formed from CYTIDINE TRIPHOSPHATE by the action of cytidylate cyclase. It is a potential cyclic nucleotide intracellular mediator of signal transductions.

A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.

A purinergic P2X neurotransmitter receptor that plays a role in pain sensation signaling and regulation of inflammatory processes.

Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.

A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly.

Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.

An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.

The relationships of groups of organisms as reflected by their genetic makeup.

An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.

Compounds that specifically inhibit PHOSPHODIESTERASE 3.

Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.

Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

A very slow opening and closing voltage-gated potassium channel that is expressed in NEURONS and is commonly mutated in BENIGN FAMILIAL NEONATAL CONVULSIONS.

Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

Use of electric potential or currents to elicit biological responses.

A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.

An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62.

The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.

The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.

A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.

An inorganic dye used in microscopy for differential staining and as a diagnostic reagent. In research this compound is used to study changes in cytoplasmic concentrations of calcium. Ruthenium red inhibits calcium transport through membrane channels.

CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.

A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.

Inorganic or organic compounds that contain boron as an integral part of the molecule.

An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.

A sesquiterpene lactone found in roots of THAPSIA. It inhibits CA(2+)-TRANSPORTING ATPASE mediated uptake of CALCIUM into SARCOPLASMIC RETICULUM.

Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.

A major class of calcium-activated potassium channels that were originally discovered in ERYTHROCYTES. They are found primarily in non-excitable CELLS and set up electrical gradients for PASSIVE ION TRANSPORT.

The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.

Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node. (1/816)

We cloned a cDNA (HAC4) that encodes the hyperpolarization-activated cation channel (If or Ih) by screening a rabbit sinoatrial (SA) node cDNA library using a fragment of rat brain If cDNA. HAC4 is composed of 1150 amino acid residues, and its cytoplasmic N- and C-terminal regions are longer than those of HAC1-3. The transmembrane region of HAC4 was most homologous to partially cloned mouse If BCNG-3 (96%), whereas the C-terminal region of HAC4 showed low homology to all HAC family members so far cloned. Northern blotting revealed that HAC4 mRNA was the most highly expressed in the SA node among the rabbit cardiac tissues examined. The electrophysiological properties of HAC4 were examined using the whole cell patch-clamp technique. In COS-7 cells transfected with HAC4 cDNA, hyperpolarizing voltage steps activated slowly developing inward currents. The half-maximal activation was obtained at -87.2 +/- 2.8 mV under control conditions and at -64.4 +/- 2.6 mV in the presence of intracellular 0.3 mM cAMP. The reversal potential was -34.2 +/- 0.9 mV in 140 mM Na+o and 5 mM K+o versus 10 mM Na+i and 145 mM K+i. These results indicate that HAC4 forms If in rabbit heart SA node. (+info)

Functional roles of aromatic residues in the ligand-binding domain of cyclic nucleotide-gated channels. (2/816)

The ligand-binding domains of cyclic nucleotide-gated (CNG) channels show sequence homology to corresponding region(s) of the Escherichia coli catabolite gene-activator protein (CAP) and to the regulatory subunit of cAMP-dependent or cGMP-dependent protein kinases. The structure of CAP and that of a cAMP-dependent protein kinases regulatory subunit have been solved, prompting efforts to generate structural models for the binding domains in CNG channel. These models explicitly predicted that an aromatic residue in the CNG channel aligning with leucine 61 of CAP forms an interaction with the bound cyclic nucleotide. We tested this hypothesis by site-directed mutagenesis in a rat olfactory channel (rOCNC1) and a bovine rod photoreceptor channel (Brcng). We found that mutations at this site had only weak effects that were not specific to the aromatic or the hydrophobic nature of the substituted residue. This result weakens the hypothesis of a strong or specific interaction at this site. We also separately mutated most of the other aromatic residues in the binding domain to alanine; most of these mutations resulted in channels that either did not function or had only minor changes in sensitivity. However, replacing tyrosine 565 with alanine (Y565A) in rOCNC1 increased agonist sensitivity by approximately 10-fold and resulted in prominent spontaneous activities. Y565 presumably lies between two alpha helices in the binding domain; one of these, the C helix, probably rotates during channel activation. The position of Y565 at the "hinge" between the C helix and another portion of the binding domain, and the consequences of Y565 mutations, strongly suggest that this portion of the binding domain is involved in channel gating processes. (+info)

Single-channel kinetics of the rat olfactory cyclic nucleotide-gated channel expressed in Xenopus oocytes. (3/816)

Cyclic nucleotide-gated channels are nonselective cation channels activated by intracellular cAMP and/or cGMP. It is not known how the binding of agonists opens the channel, or how the presumed four binding sites, one on each subunit, interact to generate cooperativity. We expressed the rat olfactory cyclic nucleotide-gated channel alpha subunit in Xenopus oocytes and recorded the single-channel currents. The channel had a single conductance state, and flickers at -60 mV showed the same power spectrum for cAMP and cGMP. At steady state, the distribution patterns of open and closed times were relatively simple, containing one or two exponential components. The conductance properties and the dwell-time distributions were adequately described by models that invoke only one or two binding events to open the channel, followed by an additional binding event that prolongs the openings and helps to explain apparent cooperativity. In a comparison between cAMP and cGMP, we find that cGMP has clearly higher binding affinity than cAMP, but only modestly higher probability of inducing the conformational transition that opens the channel. (+info)

Two pacemaker channels from human heart with profoundly different activation kinetics. (4/816)

Cardiac pacemaking is produced by the slow diastolic depolarization phase of the action potential. The hyperpolarization-activated cation current (If) forms an important part of the pacemaker depolarization and consists of two kinetic components (fast and slow). Recently, three full-length cDNAs encoding hyperpolarization-activated and cyclic nucleotide-gated cation channels (HCN1-3) have been cloned from mouse brain. To elucidate the molecular identity of cardiac pacemaker channels, we screened a human heart cDNA library using a highly conserved neuronal HCN channel segment and identified two cDNAs encoding HCN channels. The hHCN2 cDNA codes for a protein of 889 amino acids. The HCN2 gene is localized on human chromosome 19p13.3 and contains eight exons spanning approximately 27 kb. The second cDNA, designated hHCN4, codes for a protein of 1203 amino acids. Northern blot and PCR analyses showed that both hHCN2 and hHCN4 are expressed in heart ventricle and atrium. When expressed in HEK 293 cells, either cDNA gives rise to hyperpolarization-activated cation currents with the hallmark features of native If. hHCN2 and hHCN4 currents differ profoundly from each other in their activation kinetics, being fast and slow, respectively. We thus conclude that hHCN2 and hHCN4 may underlie the fast and slow component of cardiac If, respectively. (+info)

Mechanism of allosteric modulation of rod cyclic nucleotide-gated channels. (5/816)

The cyclic nucleotide-gated (CNG) channel of retinal rod photoreceptor cells is an allosteric protein whose activation is coupled to a conformational change in the ligand-binding site. The bovine rod CNG channel can be activated by a number of different agonists, including cGMP, cIMP, and cAMP. These agonists span three orders of magnitude in their equilibrium constants for the allosteric transition. We recorded single-channel currents at saturating cyclic nucleotide concentrations from the bovine rod CNG channel expressed in Xenopus oocytes as homomultimers of alpha subunits. The median open probability was 0.93 for cGMP, 0.47 for cIMP, and 0.01 for cAMP. The channels opened to a single conductance level of 26-30 pS at +80 mV. Using signal processing methods based on hidden Markov models, we determined that two closed and one open states are required to explain the gating at saturating ligand concentrations. We determined the maximum likelihood rate constants for two gating schemes containing two closed (denoted C) and one open (denoted O) states. For the C left and right arrow C left and right arrow O scheme, all rate constants were dependent on cyclic nucleotide. For the C left and right arrow O left and right arrow C scheme, the rate constants for only one of the transitions were cyclic nucleotide dependent. The opening rate constant was fastest for cGMP, intermediate for cIMP, and slowest for cAMP, while the closing rate constant was fastest for cAMP, intermediate for cIMP, and slowest for cGMP. We propose that interactions between the purine ring of the cyclic nucleotide and the binding domain are partially formed at the time of the transition state for the allosteric transition and serve to reduce the transition state energy and stabilize the activated conformation of the channel. When 1 microM Ni2+ was applied in addition to cyclic nucleotide, the open time increased markedly, and the closed time decreased slightly. The interactions between H420 and Ni2+ occur primarily after the transition state for the allosteric transition. (+info)

Sequence of events underlying the allosteric transition of rod cyclic nucleotide-gated channels. (6/816)

Activation of cyclic nucleotide-gated (CNG) ion channels involves a conformational change in the channel protein referred to as the allosteric transition. The amino terminal region and the carboxyl terminal cyclic nucleotide-binding domain of CNG channels have been shown to be involved in the allosteric transition, but the sequence of molecular events occurring during the allosteric transition is unknown. We recorded single-channel currents from bovine rod CNG channels in which mutations had been introduced in the binding domain at position 604 and/or the rat olfactory CNG channel amino terminal region had been substituted for the bovine rod amino terminal region. Using a hidden Markov modeling approach, we analyzed the kinetics of these channels activated by saturating concentrations of cGMP, cIMP, and cAMP. We used thermodynamic mutant cycles to reveal an interaction during the allosteric transition between the purine ring of the cyclic nucleotides and the amino acid at position 604 in the binding site. We found that mutations at position 604 in the binding domain alter both the opening and closing rate constants for the allosteric transition, indicating that the interactions between the cyclic nucleotide and this amino acid are partially formed at the time of the transition state. In contrast, the amino terminal region affects primarily the closing rate constant for the allosteric transition, suggesting that the state-dependent stabilizing interactions between amino and carboxyl terminal regions are not formed at the time of the transition state for the allosteric transition. We propose that the sequence of events that occurs during the allosteric transition involves the formation of stabilizing interactions between the purine ring of the cyclic nucleotide and the amino acid at position 604 in the binding domain followed by the formation of stabilizing interdomain interactions. (+info)

Rod-type cyclic nucleotide-gated cation channel is expressed in vascular endothelium and vascular smooth muscle cells. (7/816)

OBJECTIVES: Ca(++)-permeable nonselective cation channels mediate the entry of extracellular Ca++ in vascular endothelium. They are also partly responsible for Ca++ entry in vascular smooth muscle cells (SMCs). The molecular identities of these channels have not been identified. The aim of this study is to examine whether rod-type nucleotide-gated nonselective cation (CNG1) channel, a channel which has been molecularly cloned, is related to the nonselective channels in vascular cells. METHODS: We used RT-PCR, molecular cloning, northern Blot and in situ hybridization to examine the expression of CNG1 mRNA in a variety of guinea pig and rat blood vessels with different diameters and in cultured vascular endothelial cells and vascular smooth muscle cells. RESULTS: We have cloned a 402-bp partial cDNA of CNG1 channel from guinea pig mesenteric arteries. RT-PCR and southern blot results indicate that the CNG1 mRNA is expressed in both cultured vascular endothelial and cultured vascular SMCs. Northern blot revealed the transcripts of approximately 3.2 kb, approximately 5.0 kb, and approximately 1.8 kb in cultured endothelial cells. In situ hybridization yielded strong labeling in endothelium layer of aorta, medium-sized mesenteric arteries, and small mesenteric arteries. CONCLUSION: Our findings suggest a potential role of CNG protein for Ca++ entry in vascular endothelium and vascular smooth muscles. The high expression of CNG1 mRNA in the endothelium of medium-sized arteries and small-sized arteries implicates a possible involvement of CNG1 protein in the regulation of blood supply to different regions and in the regulation of arterial blood pressure. (+info)

Activity-dependent modulation of rod photoreceptor cyclic nucleotide-gated channels mediated by phosphorylation of a specific tyrosine residue. (8/816)

Cyclic nucleotide-gated (CNG) channels are crucial for phototransduction in vertebrate rod photoreceptors. The cGMP sensitivity of these channels is modulated by diffusible intracellular messengers, including Ca2+/calmodulin, contributing to negative feedback during sensory adaptation. Membrane-associated protein tyrosine kinases and phosphatases also modulate rod CNG channels, but whether this results from direct changes in the phosphorylation state of the channel protein has been unclear. Here, we show that bovine rod CNG channel alpha-subunits (bRET) contain a tyrosine phosphorylation site crucial for modulation. bRET channels expressed in Xenopus oocytes exhibit modulation, whereas rat olfactory CNG channels (rOLF) do not. Chimeric channels reveal that differences in the C terminus, containing the cyclic nucleotide-binding domain, account for this difference. One specific tyrosine in bRET (Y498) appears to be crucial; replacement of this tyrosine in bRET curtails modulation, whereas installation into rOLF confers modulability. As the channel becomes dephosphorylated, there is an increase in the rate of spontaneous openings in the absence of ligand, indicating that changes in the phosphorylation state affect the allosteric gating equilibrium. Moreover, we find that dephosphorylation, which favors channel opening, requires open channels, whereas phosphorylation, which promotes channel closing, requires closed channels. Hence, modulation by changes in tyrosine phosphorylation is activity-dependent and may constitute a positive feedback mechanism, contrasting with negative feedback systems underlying adaptation. (+info)

There are several types of channelopathies, including:

1. Long QT syndrome: This is a condition that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
2. Short QT syndrome: This is a rare condition that has the opposite effect of long QT syndrome, causing the heart to beat too quickly.
3. Catecholaminergic polymorphic ventricular tachycardia (CPVT): This is a rare disorder that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
4. Brugada syndrome: This is a condition that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
5. Wolff-Parkinson-White (WPW) syndrome: This is a condition that affects the ion channels in the heart, leading to abnormal heart rhythms and increased risk of sudden death.
6. Neuromuscular disorders: These are disorders that affect the nerve-muscle junction, leading to muscle weakness and wasting. Examples include muscular dystrophy and myasthenia gravis.
7. Dystrophinopathies: These are a group of disorders that affect the structure of muscle cells, leading to muscle weakness and wasting. Examples include Duchenne muscular dystrophy and Becker muscular dystrophy.
8. Myotonia: This is a condition that affects the muscles, causing them to become stiff and rigid.
9. Hyperkalemic periodic paralysis: This is a rare condition that causes muscle weakness and paralysis due to abnormal potassium levels in the body.
10. Hypokalemic periodic paralysis: This is a rare condition that causes muscle weakness and paralysis due to low potassium levels in the body.
11. Thyrotoxic periodic paralysis: This is a rare condition that causes muscle weakness and paralysis due to an overactive thyroid gland.
12. Hyperthyroidism: This is a condition where the thyroid gland becomes overactive, leading to increased heart rate, weight loss, and muscle weakness.
13. Hypothyroidism: This is a condition where the thyroid gland becomes underactive, leading to fatigue, weight gain, and muscle weakness.
14. Pituitary tumors: These are tumors that affect the pituitary gland, which regulates hormone production in the body.
15. Adrenal tumors: These are tumors that affect the adrenal glands, which produce hormones such as cortisol and aldosterone.
16. Carcinoid syndrome: This is a condition where cancer cells in the digestive system produce hormones that can cause muscle weakness and wasting.
17. Multiple endocrine neoplasia (MEN): This is a genetic disorder that affects the endocrine system and can cause tumors to grow in the thyroid, adrenal, and parathyroid glands.

These are just some of the many potential causes of muscle weakness. It's important to see a healthcare professional for an accurate diagnosis and appropriate treatment.

1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Explanation: Genetic predisposition to disease is influenced by multiple factors, including the presence of inherited genetic mutations or variations, environmental factors, and lifestyle choices. The likelihood of developing a particular disease can be increased by inherited genetic mutations that affect the functioning of specific genes or biological pathways. For example, inherited mutations in the BRCA1 and BRCA2 genes increase the risk of developing breast and ovarian cancer.

The expression of genetic predisposition to disease can vary widely, and not all individuals with a genetic predisposition will develop the disease. Additionally, many factors can influence the likelihood of developing a particular disease, such as environmental exposures, lifestyle choices, and other health conditions.

Inheritance patterns: Genetic predisposition to disease can be inherited in an autosomal dominant, autosomal recessive, or multifactorial pattern, depending on the specific disease and the genetic mutations involved. Autosomal dominant inheritance means that a single copy of the mutated gene is enough to cause the disease, while autosomal recessive inheritance requires two copies of the mutated gene. Multifactorial inheritance involves multiple genes and environmental factors contributing to the development of the disease.

Examples of diseases with a known genetic predisposition:

1. Huntington's disease: An autosomal dominant disorder caused by an expansion of a CAG repeat in the Huntingtin gene, leading to progressive neurodegeneration and cognitive decline.
2. Cystic fibrosis: An autosomal recessive disorder caused by mutations in the CFTR gene, leading to respiratory and digestive problems.
3. BRCA1/2-related breast and ovarian cancer: An inherited increased risk of developing breast and ovarian cancer due to mutations in the BRCA1 or BRCA2 genes.
4. Sickle cell anemia: An autosomal recessive disorder caused by a point mutation in the HBB gene, leading to defective hemoglobin production and red blood cell sickling.
5. Type 1 diabetes: An autoimmune disease caused by a combination of genetic and environmental factors, including multiple genes in the HLA complex.

Understanding the genetic basis of disease can help with early detection, prevention, and treatment. For example, genetic testing can identify individuals who are at risk for certain diseases, allowing for earlier intervention and preventive measures. Additionally, understanding the genetic basis of a disease can inform the development of targeted therapies and personalized medicine."

The term "mucolipidoses" was coined by the American pediatrician and medical geneticist Dr. Victor A. McKusick in the 1960s to describe this group of diseases. The term is derived from the Greek words "muco-," meaning mucus, and "-lipido-," meaning fat, and "-osis," meaning condition or disease.

There are several types of mucolipidoses, including:

1. Mucolipidosis type I (MLI): This is the most common form of the disorder and is caused by a deficiency of the enzyme galactocerebrosidase (GALC).
2. Mucolipidosis type II (MLII): This form of the disorder is caused by a deficiency of the enzyme sulfatases, which are necessary for the breakdown of sulfated glycosaminoglycans (sGAGs).
3. Mucolipidosis type III (MLIII): This form of the disorder is caused by a deficiency of the enzyme acetyl-CoA:beta-glucoside ceramide beta-glucosidase (CERBGL), which is necessary for the breakdown of glycosphingolipids.
4. Mucolipidosis type IV (MLIV): This form of the disorder is caused by a deficiency of the enzyme glucocerebrosidase (GUCB), which is necessary for the breakdown of glucocerebroside, a type of glycosphingolipid.

Mucolipidoses are usually diagnosed by measuring the activity of the enzymes involved in glycosphingolipid metabolism in white blood cells or fibroblasts, and by molecular genetic analysis to identify mutations in the genes that code for these enzymes. Treatment is typically focused on managing the symptoms and may include physical therapy, speech therapy, and other supportive care measures. Bone marrow transplantation has been tried in some cases as a potential treatment for mucolipidosis, but the outcome has been variable.

Prognosis: The prognosis for mucolipidoses is generally poor, with most individuals with the disorder dying before the age of 10 years due to severe neurological and other complications. However, with appropriate management and supportive care, some individuals with milder forms of the disorder may survive into adulthood.

Epidemiology: Mucolipidoses are rare disorders, with an estimated prevalence of 1 in 100,000 to 1 in 200,000 births. They affect both males and females equally, and there is no known geographic or ethnic predilection.

Clinical features: The clinical features of mucolipidoses vary depending on the specific type of disorder and the severity of the mutation. Common features include:

* Delayed development and intellectual disability
* Seizures
* Vision loss or blindness
* Hearing loss or deafness
* Poor muscle tone and coordination
* Increased risk of infections
* Coarsening of facial features
* Enlarged liver and spleen
* Abnormalities of the heart, including ventricular septal defect and atrial septal defect

Diagnosis: Diagnosis of mucolipidoses is based on a combination of clinical features, laboratory tests, and genetic analysis. Laboratory tests may include measurement of enzyme activity in white blood cells, urine testing, and molecular genetic analysis.

Treatment and management: There is no cure for mucolipidoses, but treatment and management strategies can help manage the symptoms and improve quality of life. These may include:

* Physical therapy to improve muscle tone and coordination
* Speech therapy to improve communication skills
* Occupational therapy to improve daily living skills
* Anticonvulsant medications to control seizures
* Supportive care to manage infections and other complications
* Genetic counseling to discuss the risk of inheritance and options for family planning.

Prognosis: The prognosis for mucolipidoses varies depending on the specific type and severity of the condition. In general, the prognosis is poor for children with more severe forms of the disorder, while those with milder forms may have a better outlook. With appropriate management and supportive care, some individuals with mucolipidoses can lead relatively normal lives, while others may require ongoing medical care and assistance throughout their lives.

The QT interval is a measure of the time it takes for the ventricles to recover from each heartbeat and prepare for the next one. In people with LQTS, this recovery time is prolonged, which can disrupt the normal rhythm of the heart and increase the risk of arrhythmias.

LQTS is caused by mutations in genes that encode proteins involved in the cardiac ion channels, which regulate the flow of ions into and out of the heart muscle cells. These mutations can affect the normal functioning of the ion channels, leading to abnormalities in the electrical activity of the heart.

Symptoms of LQTS can include palpitations, fainting spells, and seizures. In some cases, LQTS can be diagnosed based on a family history of the condition or after a sudden death in an otherwise healthy individual. Other tests, such as an electrocardiogram (ECG), echocardiogram, and stress test, may also be used to confirm the diagnosis.

Treatment for LQTS typically involves medications that regulate the heart's rhythm and reduce the risk of arrhythmias. In some cases, an implantable cardioverter-defibrillator (ICD) may be recommended to monitor the heart's activity and deliver an electric shock if a potentially life-threatening arrhythmia is detected. Lifestyle modifications, such as avoiding stimuli that trigger symptoms and taking precautions during exercise and stress, may also be recommended.

In summary, Long QT syndrome is a rare inherited disorder that affects the electrical activity of the heart, leading to an abnormal prolongation of the QT interval and an increased risk of irregular and potentially life-threatening heart rhythms. It is important for individuals with LQTS to be closely monitored by a healthcare provider and to take precautions to manage their condition and reduce the risk of complications.

Examples of inborn errors of renal tubular transport include:

1. Cystinuria: This is a disorder that affects the reabsorption of cystine, an amino acid, in the renal tubules. It can lead to the formation of cystine stones in the kidneys.
2. Lowe syndrome: This is a rare genetic disorder that affects the transport of sodium and potassium ions across the renal tubules. It can cause a range of symptoms, including delayed development, intellectual disability, and seizures.
3. Glycine encephalopathy: This is a rare genetic disorder that affects the transport of glycine, an amino acid, across the renal tubules. It can cause a range of symptoms, including muscle weakness, developmental delays, and seizures.
4. Hartnup disease: This is a rare genetic disorder that affects the transport of tryptophan, an amino acid, across the renal tubules. It can cause a range of symptoms, including diarrhea, weight loss, and skin lesions.
5. Maple syrup urine disease: This is a rare genetic disorder that affects the transport of branched-chain amino acids (leucine, isoleucine, and valine) across the renal tubules. It can cause a range of symptoms, including seizures, developmental delays, and kidney damage.

Inborn errors of renal tubular transport can be diagnosed through a combination of clinical evaluation, laboratory tests, and genetic analysis. Treatment depends on the specific disorder and may include dietary modifications, medications, and dialysis. Early detection and treatment can help manage symptoms and prevent complications.

Insulinoma is a rare type of pancreatic tumor that produces excess insulin, leading to low blood sugar levels. These tumors are typically benign and can be treated with surgery or medication.

Insulinomas account for only about 5% of all pancreatic neuroendocrine tumors. They usually occur in the head of the pancreas and can cause a variety of symptoms, including:

1. Hypoglycemia (low blood sugar): The excess insulin produced by the tumor can cause blood sugar levels to drop too low, leading to symptoms such as shakiness, dizziness, confusion, and rapid heartbeat.
2. Hyperinsulinism (elevated insulin levels): In addition to hypoglycemia, insulinomas can also cause elevated insulin levels in the blood.
3. Abdominal pain: Insulinomas can cause abdominal pain and discomfort.
4. Weight loss: Patients with insulinomas may experience unexplained weight loss.
5. Nausea and vomiting: Some patients may experience nausea and vomiting due to the hypoglycemia or other symptoms caused by the tumor.

Insulinomas are usually diagnosed through a combination of imaging tests such as CT scans, MRI scans, and PET scans, and by measuring insulin and C-peptide levels in the blood. Treatment options for insulinomas include surgery to remove the tumor, medications to control hypoglycemia and hyperinsulinism, and somatostatin analogs to reduce hormone secretion.

Insulinoma is a rare and complex condition that requires careful management by a multidisciplinary team of healthcare professionals, including endocrinologists, surgeons, and radiologists. With appropriate treatment, most patients with insulinomas can experience long-term remission and improved quality of life.

Neuroblastoma is caused by a genetic mutation that affects the development and growth of nerve cells. The cancerous cells are often sensitive to chemotherapy, but they can be difficult to remove surgically because they are deeply embedded in the nervous system.

There are several different types of neuroblastoma, including:

1. Infantile neuroblastoma: This type of neuroblastoma occurs in children under the age of one and is often more aggressive than other types of the cancer.
2. Juvenile neuroblastoma: This type of neuroblastoma occurs in children between the ages of one and five and tends to be less aggressive than infantile neuroblastoma.
3. Adult neuroblastoma: This type of neuroblastoma occurs in adults and is rare.
4. Metastatic neuroblastoma: This type of neuroblastoma has spread to other parts of the body, such as the bones or liver.

Symptoms of neuroblastoma can vary depending on the location and size of the tumor, but they may include:

* Abdominal pain
* Fever
* Loss of appetite
* Weight loss
* Fatigue
* Bone pain
* Swelling in the abdomen or neck
* Constipation
* Increased heart rate

Diagnosis of neuroblastoma typically involves a combination of imaging tests, such as CT scans and MRI scans, and biopsies to confirm the presence of cancerous cells. Treatment for neuroblastoma usually involves a combination of chemotherapy, surgery, and radiation therapy. The prognosis for neuroblastoma varies depending on the type of cancer, the age of the child, and the stage of the disease. In general, the younger the child and the more aggressive the treatment, the better the prognosis.

There are several different types of pain, including:

1. Acute pain: This type of pain is sudden and severe, and it usually lasts for a short period of time. It can be caused by injuries, surgery, or other forms of tissue damage.
2. Chronic pain: This type of pain persists over a long period of time, often lasting more than 3 months. It can be caused by conditions such as arthritis, fibromyalgia, or nerve damage.
3. Neuropathic pain: This type of pain results from damage to the nervous system, and it can be characterized by burning, shooting, or stabbing sensations.
4. Visceral pain: This type of pain originates in the internal organs, and it can be difficult to localize.
5. Psychogenic pain: This type of pain is caused by psychological factors such as stress, anxiety, or depression.

The medical field uses a range of methods to assess and manage pain, including:

1. Pain rating scales: These are numerical scales that patients use to rate the intensity of their pain.
2. Pain diaries: These are records that patients keep to track their pain over time.
3. Clinical interviews: Healthcare providers use these to gather information about the patient's pain experience and other relevant symptoms.
4. Physical examination: This can help healthcare providers identify any underlying causes of pain, such as injuries or inflammation.
5. Imaging studies: These can be used to visualize the body and identify any structural abnormalities that may be contributing to the patient's pain.
6. Medications: There are a wide range of medications available to treat pain, including analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and muscle relaxants.
7. Alternative therapies: These can include acupuncture, massage, and physical therapy.
8. Interventional procedures: These are minimally invasive procedures that can be used to treat pain, such as nerve blocks and spinal cord stimulation.

It is important for healthcare providers to approach pain management with a multi-modal approach, using a combination of these methods to address the physical, emotional, and social aspects of pain. By doing so, they can help improve the patient's quality of life and reduce their suffering.

There are two main types of myotonia:

1. Thomsen's disease: This is an inherited form of myotonia that affects the muscles of the face, neck, and limbs. It is caused by mutations in the CLCN1 gene and can be severe, causing difficulty with speaking, swallowing, and breathing.
2. Becker's muscular dystrophy: This is a form of muscular dystrophy that affects both the skeletal and cardiac muscles. It is caused by mutations in the DMPK gene and can cause myotonia, muscle weakness, and heart problems.

The symptoms of myotonia can vary depending on the severity of the condition and may include:

* Muscle stiffness and rigidity
* Spasms or twitches
* Difficulty with movement and mobility
* Fatigue and weakness
* Cramps
* Muscle wasting

Myotonia can be diagnosed through a combination of physical examination, medical history, and diagnostic tests such as electromyography (EMG) and muscle biopsy. There is no cure for myotonia, but treatment options may include:

* Physical therapy to improve movement and mobility
* Medications to relax muscles and reduce spasms
* Lifestyle modifications such as avoiding triggers and taking regular breaks to rest
* Surgery in severe cases to release or lengthen affected muscles.

It is important to note that myotonia can be a symptom of other underlying conditions, so proper diagnosis and management by a healthcare professional is essential to determine the best course of treatment.

Distler M, Biel M, Flockerzi V, Hofmann F (1995). "Expression of cyclic nucleotide-gated cation channels in non-sensory tissues ... Cyclic nucleotide gated channel alpha 2, also known as CNGA2, is a human gene encoding an ion channel protein. Cyclic ... "Entrez Gene: CNGA2 cyclic nucleotide gated channel alpha 2". Trudeau MC, Zagotta WN (2003). "Calcium/calmodulin modulation of ... Sautter A, Zong X, Hofmann F, Biel M (1998). "An isoform of the rod photoreceptor cyclic nucleotide-gated channel beta subunit ...

https://en.wikipedia.org/wiki/Cyclic_nucleotide-gated_channel_alpha_2

Cyclic nucleotide-gated cation channel alpha-3 is a protein that in humans is encoded by the CNGA3 gene. This gene encodes a ... Distler M, Biel M, Flockerzi V, Hofmann F (November 1994). "Expression of cyclic nucleotide-gated cation channels in non- ... member of the cyclic nucleotide-gated cation channel protein family, which is required for normal vision and olfactory signal ... "Entrez Gene: CNGA3 cyclic nucleotide gated channel alpha 3". Kohl S, Marx T, Giddings I, Jägle H, Jacobson SG, Apfelstedt-Sylla ...

https://en.wikipedia.org/wiki/Cyclic_nucleotide-gated_channel_alpha_3

"Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels". Nature. 452 (7190): 1007- ... "Insect olfactory receptors are heteromeric ligand-gated ion channels". Nature. 452 (7190): 1002-6. doi:10.1038/nature06850. ...

https://en.wikipedia.org/wiki/Insect_olfactory_receptor

Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature, 452(7190), 1007- ...

https://en.wikipedia.org/wiki/Bill_S._Hansson

1993). "A new subunit of the cyclic nucleotide-gated cation channel in retinal rods". Nature. 362 (6422): 764-7. Bibcode: ... Cyclic nucleotide gated channel beta 1, also known as CNGB1, is a human gene encoding an ion channel protein. Cyclic nucleotide ... "Entrez Gene: CNGB1 cyclic nucleotide gated channel beta 1". Hofmann F, Biel M, Kaupp UB (2006). "International Union of ... Trudeau MC, Zagotta WN (2002). "Mechanism of calcium/calmodulin inhibition of rod cyclic nucleotide-gated channels". Proc. Natl ...

https://en.wikipedia.org/wiki/CNGB1

Cyclic nucleotide-gated cation channel alpha-4 is a protein that in humans is encoded by the CNGA4 gene. CNGA4 is a modulatory ... "Entrez Gene: CNGA4 cyclic nucleotide gated channel alpha 4". Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing ... Sautter A, Zong X, Hofmann F, Biel M (1998). "An isoform of the rod photoreceptor cyclic nucleotide-gated channel β subunit ... Cyclic nucleotide-gated ion channel GRCh38: Ensembl release 89: ENSG00000132259 - Ensembl, May 2017 GRCm38: Ensembl release 89 ...

https://en.wikipedia.org/wiki/Cyclic_nucleotide-gated_channel_alpha_4

"Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate ... Cyclic nucleotide-gated ion channel GRCh38: Ensembl release 89: ENSG00000164588 - Ensembl, May 2017 GRCm38: Ensembl release 89 ... Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 is a protein that in humans is encoded by the ... "Entrez Gene: HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1". Marionneau C, Couette B, Liu J, Li ...

https://en.wikipedia.org/wiki/HCN1

Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. Two such cations channels have been fully ... Yau, K. W. (1994). "Cyclic nucleotide-gated channels: An expanding new family of ion channels". Proceedings of the National ... Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues. The best studied of these ... cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. The ...

https://en.wikipedia.org/wiki/Cyclic_nucleotide-binding_domain

"Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate ... "Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and ... Cyclic nucleotide-gated ion channel GRCh38: Ensembl release 89: ENSG00000099822 - Ensembl, May 2017 GRCm38: Ensembl release 89 ... Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 is a protein that in humans is encoded by ...

https://en.wikipedia.org/wiki/HCN2

Cyclic nucleotide-gated channels (CNGCs) are functional protein channels in the plasma membrane that have overlapping CaM ... Chao SH, Suzuki Y, Zysk JR, Cheung WY (July 1984). "Activation of calmodulin by various metal cations as a function of ionic ... The Ca2+ channels, such as the ryanodine receptor of the sarcoplasmic reticulum, can be inhibited by calmodulin bound to ... It does this by binding various targets in the cell including a large number of enzymes, ion channels, aquaporins and other ...

https://en.wikipedia.org/wiki/Calmodulin

... channels belong to the superfamily of voltage-gated K+ (Kv) and cyclic nucleotide-gated (CNG) channels. HCN channels are ... channels are integral membrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of ... by cyclic nucleotides (cAMP, cGMP, cCMP). Binding of cyclic nucleotides lowers the threshold potential of HCN channels, thus ... "Cyclic Nucleotide Regulated Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...

https://en.wikipedia.org/wiki/HCN_channel

Distler M, Biel M, Flockerzi V, Hofmann F (November 1994). "Expression of cyclic nucleotide-gated cation channels in non- ... Cyclic nucleotide-gated channel alpha 1, also known as CNGA1, is a human gene encoding an ion channel protein. Heterologously ... "A new subunit of the cyclic nucleotide-gated cation channel in retinal rods". Nature. 362 (6422): 764-767. Bibcode:1993Natur. ... "Entrez Gene: CNGA1 cyclic nucleotide gated channel alpha 1". Ncbi.nlm.nih.gov. Retrieved 2016-08-02. Kaupp, U. Benjamin; ...

https://en.wikipedia.org/wiki/Cyclic_nucleotide-gated_channel_alpha_1

"Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel". Proceedings of the National Academy ... "Voltage-gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. These ... "Distinct gating mechanisms revealed by the structures of a multi-ligand gated K(+) channel". eLife. 1: e00184. doi:10.7554/ ...

https://en.wikipedia.org/wiki/Cation_channel_superfamily

cAMP, which is the second messenger here, opens a cyclic nucleotide-gated ion channel (CNG), producing an influx of cations ( ... The Ca2+ in turn opens a Ca2+-activated chloride channel, leading to efflux of Cl−, further depolarizing the cell and ... A calcium-calmodulin complex also acts to inhibit the binding of cAMP to the cAMP-dependent channel, thus contributing to ... This mechanism of transduction is somewhat unusual, in that cAMP works by directly binding to the ion channel rather than ...

https://en.wikipedia.org/wiki/Sense_of_smell

... increasing cyclic AMP (cAMP) concentration inside a cell, which then opens a cyclic nucleotide gated cation channel. The influx ... Chen TY, Yau KW (April 1994). "Direct modulation by Ca(2+)-calmodulin of cyclic nucleotide-activated channel of rat olfactory ... because Ca2+/calmodulin-dependent protein kinase II or CaMK activation directly represses the opening of cation channels, ... of Ca2+ ions through this channel triggers olfactory adaptation immediately ...

https://en.wikipedia.org/wiki/Olfactory_fatigue

Cyclic nucleotide-gated channels: This superfamily of channels contains two families: the cyclic nucleotide-gated (CNG) ... Proton channels Voltage-gated proton channels Non-selective cation channels: These non-selectively allow many types of cations ... cyclic nucleotide-gated (HCN) channels. This grouping is functional rather than evolutionary. Cyclic nucleotide-gated channels ... Hyperpolarization-activated cyclic nucleotide-gated channels Temperature-gated channels: Members of the transient receptor ...

https://en.wikipedia.org/wiki/Ion_channel

It is still not known why the absence of cGMP-gated cation channels causes photoreceptor degradation. Mutations causing RP have ... Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel ... alpha 2 Cyclic nucleotide-gated channel alpha 3 Cyclic nucleotide-gated channel alpha 4 Cyclic nucleotide gated channel beta- ... Cyclic nucleotide-gated channel beta 1 Cyclic nucleotide-gated channel beta 3 The structure of the pore is similar to other ion ...

https://en.wikipedia.org/wiki/Cyclic_nucleotide–gated_ion_channel

Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel alpha 2 Cyclic nucleotide-gated channel alpha 3 Cyclic ... Society for Biomechanics Cardiolipin Carlos Chagas Filho Carrier protein CatSper1 CatSper2 CatSper3 CatSper4 Cation channels of ... nucleotide-gated channel alpha 4 Cyclic nucleotide-gated ion channel Cyclic nucleotide gated channel beta 3 Cys-loop receptors ... channel Voltage-gated ion channel Voltage-gated potassium channel Voltage-gated potassium channel database Voltage-gated proton ...

https://en.wikipedia.org/wiki/Index_of_biophysics_articles

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 is a protein that in humans is encoded by the ... 1998). "A family of hyperpolarization-activated mammalian cation channels". Nature. 393 (6685): 587-91. Bibcode:1998Natur.393.. ... Cyclic nucleotide-gated ion channel ENSG00000263324 GRCh38: Ensembl release 89: ENSG00000143630, ENSG00000263324 - Ensembl, May ... "Entrez Gene: HCN3 hyperpolarization activated cyclic nucleotide-gated potassium channel 3". Santoro B, Grant SG, Bartsch D, ...

https://en.wikipedia.org/wiki/HCN3

Hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels) are located mainly in pacemaker cells, these ... cation (positively charged ions) channels conduct more current as the membrane potential becomes more negative (hyperpolarised ... referred to as HCN channels (Hyperpolarization-activated cyclic nucleotide-gated). These channels open at very negative ... Because some of the voltage-gated sodium ion channels have recovered and the voltage-gated potassium ion channels remain open, ...

https://en.wikipedia.org/wiki/Cardiac_action_potential

... cyclic nucleotide-gated (HCN) channels, the molecular components of "funny" channels cloned in the late 90's, are today known ... "Hyperpolarization-activated cation channels: from genes to function". Physiological Reviews. 89 (3): 847-885. doi:10.1152/ ... "C terminus-mediated control of voltage and cAMP gating of hyperpolarization-activated cyclic nucleotide-gated channels". The ... "Hyperpolarization-activated cyclic nucleotide-gated channel 1 is a molecular determinant of the cardiac pacemaker current I(f ...

https://en.wikipedia.org/wiki/Dario_DiFrancesco

... nucleotide cGMP was able to directly regulate a new assort of membrane channels now called the nucleotide-gated cation channels ... Cyclic guanosine monophosphate (cGMP) plays an important role in visual transductions. This fact was well rooted when Fesenko ...

https://en.wikipedia.org/wiki/Transduction_(psychology)

Sanders also had influence in the investigation into the roles of plant cyclic nucleotide-gated channels that were explored at ... "A secretory pathway-localized cation diffusion facilitator confers plant manganese tolerance". Proceedings of the National ... "Nuclear-localized cyclic nucleotide-gated channels mediate symbiotic calcium oscillations". Science. 352 (6289): 1102-1105. ... To further his work on calcium channels, he then discovered that the TPC1 channel is the major pathway for ion exchange across ...

https://en.wikipedia.org/wiki/Dale_Sanders

A second strategy is to combine a cyclic nucleotide gated K+ channel with a photoactivated adenylyl cyclase to inhibit neuronal ... resulting in a pore which instead excluded cations in favor of anions. Other types of gated ion channels, ligand-gated and ... ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels ... Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion ...

https://en.wikipedia.org/wiki/Light-gated_ion_channel

... beta A1 Cyclic nucleotide-gated channel alpha 1 Cyclin A1 Cytochrome P450, family 1, member A1 Defensin, alpha 1 Dystrophin- ... alpha 1 Transient receptor potential cation channel, member A1 UDP glucuronosyltransferase 1 family, polypeptide A1 Urea ... alpha 1 Potassium large conductance calcium-activated channel, subfamily M, alpha 1 Proteasome (prosome, macropain) subunit, ...

https://en.wikipedia.org/wiki/List_of_A1_genes,_proteins_or_receptors

... pH gating domain of KcsA, cyclic nucleotide gating domains, and voltage gated potassium channels. N-type inactivation is ... Derebe MG, Sauer DB, Zeng W, Alam A, Shi N, Jiang Y (January 2011). "Tuning the ion selectivity of tetrameric cation channels ... Voltage-gated potassium channel - are voltage-gated ion channels that open or close in response to changes in the transmembrane ... December 2012). "Distinct gating mechanisms revealed by the structures of a multi-ligand gated K(+) channel". eLife. 1: e00184 ...

https://en.wikipedia.org/wiki/Potassium_channel

Creatine Cyclic adenosine monophosphate (cAMP) Nucleotide exchange factor Phosphagen Photophosphorylation "Adenosine 5'- ... ATP binds metal cations with high affinity. The binding constant for Mg2+ is (9554). The binding of a divalent cation, almost ... ATP is either secreted directly across the cell membrane through channel proteins or is pumped into vesicles which then fuse ... Törnroth-Horsefield, S.; Neutze, R. (December 2008). "Opening and closing the metabolite gate". Proc. Natl. Acad. Sci. USA. 105 ...

https://en.wikipedia.org/wiki/Adenosine_triphosphate

There are at least four genetic causes of achromatopsia, two of which involve cyclic nucleotide-gated ion channels (ACHM2, ... colourblindness is caused by mutations in the gene encoding the α-subunit of the cone photoreceptor cGMP-gated cation channel ... 2005). "Disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels". ... 2003). "Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters ...

https://en.wikipedia.org/wiki/Achromatopsia

The HCN channels were such a proposal; as they are cyclic nucleotide-gated channels. The two ion channels now suggested to ... Of these, transient receptor potential cation channel subfamily V member 1 (TRPV1) vanilloid receptors are responsible for the ... This G protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels. Further steps in the ... These second messengers may open gated ion channels or may cause release of internal calcium. Though all TAS2Rs are located in ...

https://en.wikipedia.org/wiki/Taste_receptor

... membrane receptors and hyperpolarization-activated cyclic-nucleotide-gated channels. For example, potassium channels and ... The most important cations for the action potential are sodium (Na+) and potassium (K+). Both of these are monovalent cations ... ligand-gated channels, and voltage-gated ion channels. For fixed ion concentrations and fixed values of ion channel conductance ... Voltage-gated ion channels, also known as voltage dependent ion channels, are channels whose permeability is influenced by the ...

https://en.wikipedia.org/wiki/Membrane_potential

cGMP phosphodiesterase breaks down cGMP, an intracellular second messenger which opens cGMP-gated cation channels. ... Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". ... Decrease in cGMP concentration leads to decreased opening of cation channels and subsequently, hyperpolarization of the ... Kroll, S.; Phillips, W. J.; Cerione, R. A. (1989). "The regulation of the cyclic GMP phosphodiesterase by the GDP-bound form of ...

https://en.wikipedia.org/wiki/Transducin

... channel family 1.A.5 Polycystin cation channel family 1.A.6 Epithelial Na+ channel family 1.A.7 ATP-gated P2X receptor cation ... cyclic Lipodepsipeptide Family 1.D.36 The Oligobornene Ion Channel Family 1.D.37 The Hibicuslide C Family 1.D.38 The Cyclic ... Phage P22 injectisome family 1.A.46 Anion channel-forming bestrophin family 1.A.47 Nucleotide-sensitive anion-selective channel ... ligand-gated ion channel family 1.A.10 Glutamate-gated ion channel family of neurotransmitter receptors 1.A.11 Ammonium channel ...

https://en.wikipedia.org/wiki/Transporter_Classification_Database

It has been shown in studies that transport of HCN (hyperpolarization activated cyclic nucleotide) gated channel isoforms to ... Neuronal Activity Influences the sub-cellular distribution of hyperpolarization-activated cation channels in hippocampal ... In this model, there is downregulation of the A-type encoding Kv4.2 channel. This channel is involved in limiting ... In the same model, the aforementioned upregulation of t-type calcium channels also has been shown to result in increased burst ...

https://en.wikipedia.org/wiki/Apical_dendrite

Nakamura, Tadashi; Gold, Geoffrey H. (1987). "A cyclic nucleotide-gated conductance in olfactory receptor cilia". Nature. 325 ( ... Depolarization in these cells result from opening of non-selective cation channels upon binding of the odorant to the specific ... Salt and sour receptors are chemically gated ion channels, which depolarize the cell. Sweet, bitter, and umami receptors are ... Mechanosensitive ion channels are found in many cell types and it has been shown that the permeability of these channels to ...

https://en.wikipedia.org/wiki/Stimulus_(physiology)

In addition to NAADP gating the channel, there is evidence that the luminal pH also affects TPC channel activity, either TPC1 [ ... Cyclic ADP-ribose IP3 Clapper, David L.; Walseth, Timothy F.; Dargie, Peter J.; Lee, Hon Cheung (1987). "Pyridine Nucleotide ... These groups therefore concluded that TPCs were cation channels that conducted both Ca2+ and Na+ (analogous to the NMDA ... that TPCs function as NAADP-gated Ca2+-permeable channels, but it cannot be formally excluded that TPCs, acting as Na+ channels ...

https://en.wikipedia.org/wiki/Nicotinic_acid_adenine_dinucleotide_phosphate

A fraction of the effects of amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct ... A single nucleotide polymorphism (SNP) in the protein NEDD4L may impact how amiloride affects a person's blood pressure in ... structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel". Pharmacological Reviews. 67 ... Cystic fibrosis is a genetic disorder due to a mutation in the CFTR gene, which encodes for the CFTR chloride channel. There is ...

https://en.wikipedia.org/wiki/Amiloride

... is a light-gated cation channel that can depolarize the cells in which it is expressed. During CEF, the Bamberg lab continued ... Seyfried P, Eiden L, Grebenovsky N, Mayer G, Heckel A (2017). "Photo-tethers for the (multi-)cyclic, conformational caging of ... In order to investigate for example the structural implications of the asymmetric nucleotide-binding domains and the trans- ... a directly light-gated cation-selective membrane channel". Proc Natl Acad Sci USA. 100 (24): 13940-5. Bibcode:2003PNAS.. ...

https://en.wikipedia.org/wiki/Cluster_of_Excellence_Frankfurt_Macromolecular_Complexes

... ion channel Calcium-activated potassium channel Cyclic nucleotide-gated ion channel Voltage-dependent calcium channel Receptor ... When the NMDA receptor is activated by the binding of two co-agonists, the cation channel opens, allowing Na+ and Ca2+ to flow ... Wikimedia Commons has media related to Ligand-gated ion channel. Ligand-Gated Ion Channel database at European Bioinformatics ... Ligand gated ion channels". HUGO Gene Nomenclature Committee. "ligand-gated channel" at Dorland's Medical Dictionary Purves, ...

https://en.wikipedia.org/wiki/Ligand-gated_ion_channel

... channel. Learn about this gene and related health conditions. ... of the cone photoreceptor cyclic nucleotide-gated (CNG) ... cone photoreceptor cGMP-gated cation channel beta-subunit. *cyclic nucleotide-gated cation channel modulatory subunit ... of the cone photoreceptor cyclic nucleotide-gated (CNG) channel. These channels are found exclusively in light-detecting ( ... cations) into cells. In cones, CNG channels remain open under dark conditions, allowing cations to flow in. When light enters ...

https://medlineplus.gov/genetics/gene/cngb3/

Cyclic Nucleotide Gated Cation Channels Cyclic Nucleotide Gated Channel Cyclic Nucleotide Gated Ion Channels Cyclic-Nucleotide ... Channel, Cyclic-Nucleotide Gated. Cng Cation Channel. Cyclic Nucleotide Gated Cation Channel. Cyclic Nucleotide Gated Cation ... Cyclic Nucleotide-Gated Cation Channel. Cyclic-Nucleotide Gated Channel. Cyclic-Nucleotide Gated Ion Channels. Gated Channel, ... Cyclic Nucleotide-Gated Cation Channel Entry term(s). Cation Channel, Cng Channel, Cng Cation Cng Cation Channel Cyclic ...

https://decs.bvsalud.org/en/ths/resource/?id=52792

BACKGROUND: Cyclic nucleotide-gated ion channels (CNGCs) are nonselective cation channels that are ubiquitous in eukaryotic ... Genome-wide identification and expression analysis of the cyclic nucleotide-gated ion channel (CNGC) gene family in Saccharum ... As Ca2+ channels, some CNGCs have also proven to be K+-permeable and involved in plant development and responses to ... Using FST analysis and genome-wide association study (GWAS), a total of 9, 23 and 9 DNA variants (single nucleotide ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=mh:Saccharum/gen%C3%A9tica

Cyclic Nucleotide-Gated Cation Channels Mediate Sodium and Calcium Influx in Rat Colon. Am J Physiol Cell Physiol. 2000 Feb;278 ... Expression of Cyclic Nucleotide-Gated Cation Channels in Airway Epithelial Cells. J Membr Biol. 1999 Sep 15;171(2):117-26. PMID ... Hormones Increase mRNA of Cyclic-nucleotide-gated Cation Channels in Airway Epithelia. Pflugers Arch 2000 Nov;441(1):69-77. ... Cardiac L-type Calcium Channel Alpha 1-subunit Is Increased by Cyclic Adenosine Monophosphate: Messenger RNA and Protein ...

https://medicine.uky.edu/departments/internalmedicine/users/swleun2

Cyclic Nucleotide-Gated Cation Channels. A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore- ... Peanut AgglutininCyclic Nucleotide-Gated Cation ChannelsInsect ProteinsZebrafish ProteinsTransient Receptor Potential Channels ... Cyclic Nucleotide Phosphodiesterases, Type 6. A cyclic nucleotide phosphodiesterase subfamily that is highly specific for ... nonselective cation channel (h), delayed rectifying potassium channel (Kv), noninactivating potassium channel (Kx) and calcium ...

https://lookformedical.com/en/search/photoreceptor-cells

I(h) Cation Channels use Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels I(h) Channels use Hyperpolarization- ... IK Potassium Channels use Intermediate-Conductance Calcium-Activated Potassium Channels IKappaB alpha use NF-KappaB Inhibitor ... Ih Cation Channels use Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels IHHNV use Densovirinae ...

https://decs.bvs.br/I/DeCS2016_Alfab-I.htm

"A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous ... Known genetic causes of this are mutations in the cone cell cyclic nucleotide-gated ion channels CNGA3 (ACHM2) and CNGB3 (ACHM3 ... There are at least four genetic causes of congenital ACHM, two of which are cyclic nucleotide-gated ion channels (ACHM2/ACHM3 ... cGMP is particularly important in visual perception as its level controls the opening of cyclic nucleotide-gated ion channels ( ...

https://www.chemeurope.com/en/encyclopedia/Achromatopsia.html

Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: ...

https://anesthesiology.weill.cornell.edu/research/publications?page=3&%3Bf%5Bauthor%5D=2191&f%5Bauthor%5D=1960&s=type&o=asc

... "cyclic nucleotide-gated cation channel 4","protein_coding" "AT5G54770","TZ","Arabidopsis thaliana","thiazole biosynthetic ... "Solute transport.channels.VIC superfamily.voltage-gated potassium cation channel (TPK/KCO-type)","protein_coding" "AMTR_ ... "cation channel (DMI1). calcium cation channel (DMI1/Pollux,Castor)","protein_coding" "Solyc09g091830.4.1","No alias","Solanum ... Channel forming colicin, C-terminal cytotoxic (InterPro:IPR000293); BEST Arabidopsis thaliana protein match is: Ribosomal ...

https://evorepro.sbs.ntu.edu.sg/go/sequences/table/5383

KATP Channels. Canales KATP. Canais de Cátion Controlados por Nucleotídeo Cíclico. Cyclic Nucleotide-Gated Cation Channels. ... Cyclic Nucleotide Phosphodiesterases, Type 7. Fosfodiesterasas de Nucleótidos Cíclicos Tipo 7. Peroxirredoxina VI. ... Cyclic Nucleotide Phosphodiesterases, Type 1. Fosfodiesterasas de Nucleótidos Cíclicos Tipo 1. Nucleotídeo Cíclico ... Cyclic Nucleotide Phosphodiesterases, Type 2. Fosfodiesterasas de Nucleótidos Cíclicos Tipo 2. Nucleotídeo Cíclico ...

https://decs2008.bvsalud.org/P/new_2008.htm

G-protein-gated or cyclic nucleotide-gated (CNG) ion channels, transient receptor potential (TRP) cation channels, and water ( ... ion channels (i.e. voltage-dependent calcium channels, inwardly rectifying potassium channels, NGF-gated Ca2+ channels), ... particularly in voltage-gated Na+ and K+ channels [93]. Targeting of ion channels is isoform-specific, as demonstrated for Kv ... and ion channels pl-VDAC (a plasmalemmal form of mitochondrial voltage gated anion channel VDAC1) and NMDAR. This ER- ...

https://www.intechopen.com/chapters/74235

Cyclic Nucleotide-Gated Cation Channels. *Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels. *Ligand-Gated Ion ... A subfamily of rhodopsin proteins that function as light-gated ion channels in GREEN ALGAE. ...

https://profiles.ouhsc.edu/display/3870

Potassium Channels Niacinamide Ankyrins Ancestry Cyclic Nucleotides Cations Anthozoa Electric Potential Difference Ctenophora ... Hyperpolarization Activated Cyclic Nucleotide Gated Channels Vertebrates Dendrites Most Recent Publications. External cd,sup,2+ ... The S6 gate in regulatory Kv6 subunits restricts heteromeric K,sup,+,/sup, channel stoichiometry. Aditya Pisupati, Keith ... Ether-à-go-go family voltage-gated K,sup,+,/sup, channels evolved in an ancestral metazoan and functionally diversified in a ...

https://www.huck.psu.edu/people/timothy-jegla

Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain. Brain Res Mol ... Jiang ZG, Pessia M, North RA (1993) Dopamine and baclofen inhibit the hyperpolarization-activated cation current in rat ventral ... channels, and h-channels. However, our data are consistent with DAergic modulation of h-channels, and not these other channels ... Drain P, Dubin AE, Aldrich RW (1994) Regulation of Shaker K+ channel inactivation gating by the cAMP-dependent protein kinase. ...

https://www.jneurosci.org/content/26/12/3229?ijkey=c232e44f8935ba8f3f59914a189217d1c33c64fc&keytype2=tf_ipsecsha

D3.633.100.759.646.454.160 Cyclic IMP D3.438.759.646.616.300 D3.633.100.759.646.616.300 Cyclic Nucleotide-Gated Cation Channels ... Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels D12.776.543.550.425.476 D12.776.543.550.450.476 Hypogravity G1.595 ... NAV1.4 Voltage-Gated Sodium Channel D12.776.543.550.425.875.750.400 D12.776.543.550.450.875.750.400 NAV1.5 Voltage-Gated Sodium ... Voltage-Dependent Anion Channels D12.776.543.550.425.730.520 D12.776.543.550.450.730.520 Voltage-Gated Sodium Channel beta ...

https://decs2017.bvsalud.org/P/mnchg2017.txt

gating behavior of ion channels. Our work has focused on cyclic nucleotide-regulated channels, channels that are gated by the ... The channel pH titration in salts of multivalent cations is particularly challenging because of the cation hydrolysis and the ... cyclic nucleotide-gated (CNG) channels important in sensory transduction and the hyperpolarization-activated, cyclic nucleotide ... Molecular mechanisms for the regulation of ion channels by cyclic nucleotides William N. Zagotta Department of Physiology and ...

http://2medicalcare.com/s/sici.umh.es1.html

Kaupp UB, Seifert R. Cyclic nucleotide-gated ion channels. Physiol Rev. 2002;82:769-824. ... the cGMP-gated channels close, reducing the influx of cations [15-17]. The change in current hyperpolarizes the cell and ... Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature. ... Fung BK, Hurley JB, Stryer L. Flow of information in the light-triggered cyclic nucleotide cascade of vision. Proc Natl Acad ...

https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-017-0171-2

Surgery to correct retractile or UDT requires relo- cation of the testes to the scrotum without tension. Unipolar non-return to ... See color insert p. Any tensile component of cyclic strain is the source of crack growth (fatigue) in materials. 1 General ... In Investigation 11-C, in darkness and under non-saturating illumination, cGMP-gated opptions mediate a sustained Ca2 influx ( ... Insecticide targets Physiologically or biochemically important molecules (such as those comprising ion channels, recep- tors, ...

http://findbinaryoption.com/covered-call-in-options-trading.html

Ho, Ivan H M and Murrell-Lagnado, R D (1999) Molecular mechanism for sodium-dependent activation of G protein-gated K+ channels ... P2X4 forms functional ATP-activated cation channels on lysosomal membranes regulated by luminal pH. Journal of Biological ... Suidan, H S, Murrell, R D and Tolkovsky, A M (1990) The rise in cyclic-AMP levels in cultured rat superior cervical-ganglion ... Nucleotide sequence of the aconitase gene and amino acid sequence similarity with mitochondrial aconitases, the iron-responsive ...

http://srodev.sussex.ac.uk/view/subjects/QH301.html

Myocardial hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are known to play a role in arrhythmogenesis ... Organic cation transporter (OCT2) localised mainly in the kidney can be responsible for renal excretion of this type of drugs ... HCN channels - diabetes mellitus - heart - electrophysiology - rat. Changes of Serum Cholinesterases Activity in Obese Wistar ... Ventricle-specific HCN2 Channels Downregulation in the Heart of Rats With Streptozotocin-induced Diabetes Mellitus ...

https://sciendo.com/article/10.2478/afpuc-2022-0009?tab=recent-articles

In addition to impaired trafficking, the mutation results in defective channel gating. Together, the reduced number of channels ... Heteroaliphatic groups may be substituted or unsubstituted, branched or unbranched, cyclic or acyclic, and include "heterocycle ... and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl ... each containing six transmembrane helices and a nucleotide binding domain. The two transmembrane domains are linked by a large ...

https://patents.justia.com/patent/8563573

Human TRPV1(Transient Receptor Potential Cation Channel Subfamily V, Member 1) ELISA Kit ... Human CAMP-Specific Cyclic Nucleotide Phosphodiesterase 8A (PDE8A) ELISA Kit. abx382131-96tests Abbexa 96 tests. ... Human P2RX7(Purinergic Receptor P2X, Ligand Gated Ion Channel 7) ELISA Kit ... Human CACNa1D(Calcium Channel, Voltage Dependent, L-Type, Alpha 1D Subunit) ELISA Kit ...

https://allelisakits.com/human-pde4dphosphodiesterase-4d-camp-specific-elisa-kit/

Plant helper immune receptors are Ca2+ -permeable nonselective cation channels. * Plant Immunity Requires Conformational ... Multilocus patterns of nucleotide diversity, population structure and linkage disequilibrium in Boechera stricta, a wild ... Redox rhythm reinforces the circadian clock to gate immune response * Reducing environmental bias when measuring natural ... FKF1 F-box protein mediates cyclic degradation of a repressor of CONSTANS in Arabidopsis ...

https://scholars.duke.edu/display/meshD017360

... droplets against gravity in large cells Restoration of visual function by expression of a light-gated mammalian ion channel in ... cations, and PEG providing a broad-spectrum, antibacterial, and antifouling surface via one-step coating Modeling the natural ... a longitudinal study Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome Cyclic peptide FXII ... photoproduct recognition by the Rad4/XPC nucleotide excision repair complex DNA translocation mechanism of the MCM complex and ...

https://regenerativemedicine.net/NewsletterArchives.asp?qEmpID=25186&qCat=RMJ

PLAZA HAIRDRYERS PIQUE TRIOS REANNEXED TOESHOES FREIGHTER CRUCIFIXION PLAYS CLITORIS SUBAGENCY OPINE SEGUING RAKED CHANNEL ... FIDEL ABBREVIATION PROTISTA FLESHING BRAZIERS CONTRAPTIONS FIATS QUAGMIRE AWAYNESS BOSKIEST ORACULARLY DRIFT TERSENESS GATED ... TANTRAS ABNEGATED MOLLY DIRECTORATES PRESYNAPTICALLY HANDYMEN OCTYL THICKEN RUNNYMEDE BLOWOUTS INTERROGATING SMUTTILY CATION ... HABANERA NONTEMPORAL POSTCARD MONOPHONIC ILLUSIONISTS SANSERIF MODULATION PREMIXED ASSORT POSTALLY INFALLIBLENESS NUCLEOTIDES ...

https://ftp.cdc.gov/pub/Health_Statistics/NCHS/Software/mmds/2003/mmds_spell.txt

The CNGB3 gene provides instructions for making one part (the beta subunit) of the cone photoreceptor cyclic nucleotide-gated (CNG) channel. (medlineplus.gov)
There are at least four genetic causes of congenital ACHM, two of which are cyclic nucleotide-gated ion channels (ACHM2/ACHM3), a third the cone photoreceptor transducin ( GNAT2 , ACHM4), and the last unknown. (chemeurope.com)

A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. (bvsalud.org)

Known genetic causes of this are mutations in the cone cell cyclic nucleotide-gated ion channels CNGA3 (ACHM2) and CNGB3 (ACHM3) as well as the cone cell transducin, GNAT2 (ACHM4). (chemeurope.com)

Most CNGB3 gene mutations prevent the production of any functional beta subunit, which alters the structure of CNG channels. (medlineplus.gov)
When expressed alone, CNGB3 cannot produce functional channels, whereas this is not the case for CNGA3 . (chemeurope.com)
Coassembly of CNGA3 and CNGB3 produces channels with altered membrane expression, ion permeability ( Na + vs. K + and Ca 2+ ), relative efficacy of cAMP/cGMP activation, decreased outward rectification, current flickering, and sensitivity to block by L-cis-diltiazem . (chemeurope.com)

CFTR is composed of approximately 1480 amino acids that encode a protein made up of a tandem repeate of transmembrane domains, each containing six transmembrane helices and a nucleotide binding domain. (justia.com)

A subfamily of rhodopsin proteins that function as light-gated ion channels in GREEN ALGAE. (ouhsc.edu)

While some mutations in CNGA3 result in truncated and, presumably, non-functional channels this is largely not the case. (chemeurope.com)
While few mutations have received in-depth study, see table 1, at least one mutation does result in functional channels. (chemeurope.com)
Functional evolution of eukaryotic ion channels and evolution of neuronal signaling and cell structure. (psu.edu)

When light enters the eye, it triggers the closure of these channels, stopping the inward flow of cations. (medlineplus.gov)

CNG channels are openings in the cell membrane that transport positively charged atoms (cations) into cells. (medlineplus.gov)
CFTR is expressed in a variety of cells types, including absorptive and secretory epithelia cells, where it regulates anion flux across the membrane, as well as the activity of other ion channels and proteins. (justia.com)

The two transmembrane domains are linked by a large, polar, regulatory (R)-domain with multiple phosphorylation sites that regulate channel activity and cellular trafficking. (justia.com)

Because these CNG channels are specific to cones, rods are generally unaffected by this disorder. (medlineplus.gov)

Complete achromatopsia is genetically heterogeneous and segregates with mutations in CNGA3 or CNGB3 genes, which respectively encode for alpha- and beta-subunits of the cyclic-nucleotide-gated (CNG) cation channel expressed in cone photoreceptors. (nih.gov)

The severely truncated beta-subunit is likely to render a nonfunctional cone CNG channel and cause total colour blindness in this kindred. (nih.gov)
The CNGB3 gene provides instructions for making one part (the beta subunit) of the cone photoreceptor cyclic nucleotide-gated (CNG) channel. (medlineplus.gov)
Most CNGB3 gene mutations prevent the production of any functional beta subunit, which alters the structure of CNG channels. (medlineplus.gov)

they express numerous voltage-gated sodium, calcium, potassium, and chloride channels and fire action potentials spontaneously, accompanied by a rise in intracellular calcium. (nih.gov)

Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. (nih.gov)

The ongoing experiments are also focused on characterization of electrical status of pituitary stem cells and single cell heterogeneity of electrical activity during development combined with analysis of expression of selected ion channel genes. (nih.gov)

We also identified channels accounting for resting membrane potentials and spiking depolarization, as well as the mechanism for bursting and repolarization and channels involved, focusing on the role of calcium-controlled potassium channels in these processes. (nih.gov)

The resulting channels are nonfunctional and prevent cones from carrying out phototransduction. (medlineplus.gov)

SC, Mount DB, Gamba G. Molecular physiology of cation -coupled Cl- cotransport: the SLC12 family. (nih.gov)

CNG channels are openings in the cell membrane that transport positively charged atoms (cations) into cells. (medlineplus.gov)
This change in cation transport alters the cone's electrical charge, which ultimately generates a signal that is interpreted by the brain as vision. (medlineplus.gov)

These channels are found exclusively in light-detecting (photoreceptor) cells called cones, which are located in a specialized tissue at the back of the eye known as the retina. (medlineplus.gov)

This symposium will dissect and review the parcellation of cAMP signaling in the nervous system based on the anatomical diversity of expression of Gs-coupled GPCRs, cAMP sensors, cyclic nucleotide phosphodiesterases, and cyclic nucleotide-gated cation channels, and discuss how new imaging methods, high-throughput screening, and high-content screening have transformed this field, ripening it for translational research and drug discovery. (nih.gov)

Anatomy17

Organisms10

Chemicals and Drugs167

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Phenomena and Processes43

Disciplines and Occupations2

Technology, Industry, Agriculture1

Information Science4

Health Care1

Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node. (1/816)

Functional roles of aromatic residues in the ligand-binding domain of cyclic nucleotide-gated channels. (2/816)

Single-channel kinetics of the rat olfactory cyclic nucleotide-gated channel expressed in Xenopus oocytes. (3/816)

Two pacemaker channels from human heart with profoundly different activation kinetics. (4/816)

Mechanism of allosteric modulation of rod cyclic nucleotide-gated channels. (5/816)

Sequence of events underlying the allosteric transition of rod cyclic nucleotide-gated channels. (6/816)

Rod-type cyclic nucleotide-gated cation channel is expressed in vascular endothelium and vascular smooth muscle cells. (7/816)

Activity-dependent modulation of rod photoreceptor cyclic nucleotide-gated channels mediated by phosphorylation of a specific tyrosine residue. (8/816)

Nucleotides, Cyclic

Ion Channels

Cations

TRPM Cation Channels

Cyclic Nucleotide Phosphodiesterases, Type 1

Calcium Channels

Cyclic GMP

TRPC Cation Channels

Cyclic Nucleotide-Gated Cation Channels

3',5'-Cyclic-AMP Phosphodiesterases

Nucleotides

Ion Channel Gating

2',3'-Cyclic-Nucleotide Phosphodiesterases

Cyclic AMP

TRPV Cation Channels

Cations, Divalent

Cyclic Nucleotide Phosphodiesterases, Type 3

Molecular Sequence Data

Calcium

Phosphoric Diester Hydrolases

Potassium Channels, Inwardly Rectifying

Phosphodiesterase Inhibitors

Calcium Channel Blockers

Cyclic Nucleotide Phosphodiesterases, Type 2

Cations, Monovalent

Chloride Channels

Amino Acid Sequence

Potassium Channel Blockers

Dibutyryl Cyclic GMP

Membrane Potentials

Kinetics

Patch-Clamp Techniques

Cyclic Nucleotide Phosphodiesterases, Type 4

Transient Receptor Potential Channels

Electrophysiology

Electric Conductivity

Potassium Channels, Voltage-Gated

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels

Calcium Channels, L-Type

Flufenamic Acid

Adenosine Triphosphate

TRPP Cation Channels

Acid Sensing Ion Channels

Potassium

1-Methyl-3-isobutylxanthine

KATP Channels

3',5'-Cyclic-GMP Phosphodiesterases

Potassium Channels, Calcium-Activated

Cyclic Nucleotide Phosphodiesterases, Type 7

Sodium

Cells, Cultured

Oocytes

Cell Line

Sodium Channel Blockers

Cell Membrane

Mutation

Magnesium

Adenine Nucleotides

Cyclic Nucleotide Phosphodiesterases, Type 5

Cloning, Molecular

Bucladesine

Calmodulin

Base Sequence

Cyclic IMP

Binding Sites

Ion Transport

Epithelial Sodium Channels

Shaker Superfamily of Potassium Channels

Theophylline

Xenopus laevis

Dose-Response Relationship, Drug

Polymorphism, Single Nucleotide

Calcium Channels, N-Type

Large-Conductance Calcium-Activated Potassium Channels

Protein Structure, Tertiary

Calcium Channels, T-Type

Xenopus

Ether-A-Go-Go Potassium Channels

Guanine Nucleotides

Barium