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)

TY - JOUR. T1 - Cyclic nucleotide-gated cation channel expression in embryonic chick brain. AU - Timpe, Leslie C.. AU - Jin, Kun Lin. AU - Puelles, Luis. AU - Rubenstein, John L.R.. N1 - Funding Information: We thank Brian Williams, PhD, for his advice and Ms. Katherine A. Logee for technical support. This work was supported by NIH Grant PO1 HL43821 and the Dept. of Veterans Affairs.. PY - 1999/3/20. Y1 - 1999/3/20. N2 - Cyclic nucleotide-gated cation channels mediate sensory transduction in vertebrate photoreceptors and olfactory epithelium. These channels are also present in some non-sensory cells, but little is known of their physiOlOgiCal roles outside sensory systems. Using in situ hybridization we found that cyclic nucleotide channel mRNA is expressed specifically in the embryonic chicken forebrain, thalamus, optic tectum, basal midbrain and hindbrain, as well as in the branchial arches, limb buds and skin. Cyclic nucleotide gated channels may thus contribute to development or to cellular ...
Second messenger, cAMP, causes the opening of cation-selective cyclic nucleotide-gated (CNG) channels and depolarization of the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory subunit of this channel which is known to play a central role in the transduction of odorant signals and subsequent adaptation. By accelerating the calcium-mediated negative feedback in olfactory signaling it allows rapid adaptation to odor stimulation and extends its range of odor detection (By similarity).
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene. There are four HCN channels. HCN4 is prominently expressed in the pace maker region of the mammalian heart. Some humans with bradycardia and Sick sinus syndrome have been shown to have mutations in their HCN4 gene. The role of HCN channels in autonomic control of heart rate is currently a matter of ongoing investigation. HCN4 has been shown to interact with HCN2. Cyclic nucleotide-gated ion channel Funny current GRCh38: Ensembl release 89: ENSG00000138622 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000032338 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M (May 1999). Two pacemaker channels from human heart with profoundly different activation kinetics. The EMBO Journal. 18 (9): 2323-9. doi:10.1093/emboj/18.9.2323. PMC 1171315 . PMID 10228147. Seifert R, Scholten A, ...
The HCN channels form the subgroup of cyclic nucleotide-gated cation channel within the large superfamily of the pore loop cation channels. Like other pore loop channels, HCN channels are complexes consisting of 4 subunits that are arranged around the ventral pore. Each HCN channe subunit consists of 3 principal structural ovules: the transmembrane core and the cystosolic amino (N) terminal and carboxyl © terminal domains. The transmembrane core is comosed of 6 transmembrane segments (S1-S6) including a positively charged voltage sensor (S4) and the ion conducting pore region between (S5 and S6. The proximal portion of the systolic C-terminal domain contains the cyclic nucleotide binding domain (CNBD), which mediates modulation by cyclic nucleotides. A highly conserved asparagine residue in the extracellular loop between S5 and the pore loop is glycosylated; this posttranstional channel modification is crucial for normal cell surface expression [1690]. ...
Cyclic nucleotide-gated (CNG) channels mediate the transduction of light signals to electrical signals in vertebrate photoreceptors. These channels are non-selective for cations and open upon cGMP binding. The intracellular cGMP concentration is elevated in darkness, and the current through CNG channels maintains the membrane of the rod photoreceptor at around -40 mV. When light enters the retina, it triggers a signal transduction cascade that decreases intracellular cGMP, and therefore CNG channels close. A reduction in CNG current hyperpolarizes the rod. Two molecular mechanisms are crucial for the proper physiological function of retinal CNG channels. First, block of these channels by physiological agents reduces membrane noise in rods. This feature enables rods to detect photons with high sensitivity. Second, CNG channels must be able to conduct current in response to the light-triggered changes in intracellular cGMP. In other words, they should open and close gradually in response to cGMP
Cyclic nucleotide-gated (CNG)1 ion channels are key players in visual and olfactory signal transduction pathways (reviewed in Lancet, 1986; Yau and Baylor, 1989; Zufall et al., 1994). Although they are only weakly voltage dependent, CNG channels have regions of sequence similarity with voltage-gated channels (Jan and Jan, 1990). One region of high conservation between CNG channels and voltage-gated channels is the P region, thought to line a portion of the ion-conducting pore. Shaker K+ channels that have had portions of their P region replaced with the corresponding region from CNG channels take on many of the permeation properties of CNG channels (Heginbotham et al., 1992). These chimeric channels become permeable to Na+ as well as to K+ and become blocked by the divalent cations Mg2+ and Ca2+. Like voltage-gated channels, CNG channels are thought to possess multi-ion pores (Furman and Tanaka, 1990; Sesti et al., 1995). The external divalent cation binding site is thought to involve the E363 ...
Ca2+ signaling is central to many aspects of plant physiology; however, the channels involved in mediating Ca2+ fluxes in plants remain largely elusive. This is at least partially due to the absence of plant homologs to many of the well-characterized Ca2+ channels present in animals. Instead, plants have expanded families of ligand-gated, non-specific cation channels such as the cyclic nucleotide-gated channels (CNGCs) and glutamate receptor-like channels (GLRs), which are hypothesized to provide Ca2+ channel function in plants. The 20 member CNGC family represents one of two large families of putative Ca2+ channels in Arabidopsis, and various isoforms have been implicated in plant development and stress-response signaling, including immunity. Among Arabidopsis CNGC mutants, cpr22 and dnd1 are the best characterized mutants that show similar autoimmunity phenotypes such as constitutive expression of PR genes and heightened accumulation of salicylic acid. To understand the regulation of plant ...
Dr. Chen earned his medical degree at National Yang-Ming University in 1986 in Taiwan and his Ph.D. at Johns Hopkins University Medical School in 1994. He then received postdoctoral training at Brandeis University (1994-1996) and spent 4 years (1996-2000) as teaching faculty at National Yang-Ming University before joining UC Davis in 2001.. During his graduate studies at Hopkins, Dr. Chen worked under Professor King-Wai Yau in the Department of Neuroscience. He discovered calmodulin modulation of cyclic nucleotide-gated cation channels critical in visual and olfactory sensory adaptation mechanisms. The discovery opened the field of calmodulin modulation of ion channels.. During his postdoctoral training at Brandeis, Dr. Chen examined the biophysical mechanism of CLC chloride channels. Since then, Dr. Chen has been well known in the field of chloride channels. He received Paul Cranefield award from Society for General Physiologists in 2004. His laboratory currently studies various ion channels, ...
Additional file 5: of A comparison of heat-stress transcriptome changes between wild-type Arabidopsis pollen and a heat-sensitive mutant harboring a knockout of cyclic nucleotide-gated cation channel 16 (cngc16)
Xi-Qin Deng, Associate Professor of Cell Biology, and the Joanne I Moore Professor of Pharmacology at University of Oklahoma Health Sciences Center will be delivering a seminar on cGMP/PKG signaling regulation of endoplasmic reticulum homeostasis in CNG channel deficiency on Wednesday, January 24th at 12:00 Noon in the Moran Eye Center auditorium.. Abstract: Mutations in the CNGA3 and CNGB3 genes that encode the cone cyclic nucleotide-gated (CNG) channel subunits account for about 80% of all cases of achromatopsia and are associated with progressive cone dystrophies. Cone photoreceptors degenerate over time in patients and in mouse models of CNG channel deficiency. Over the last several years, my laboratory has been investigating the cellular mechanisms of cone degeneration using mouse models with CNG channel deficiency. Upon binding of cyclic guanosine monophosphate (cGMP) under dark conditions, CNG channels open and permit the influx of the calcium and sodium ions necessary to maintain the ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Prenatal Expressions of Hyperpolarization-activated Cyclic-Nucleotide-Gated Channel (HCN) Genes in Dysplastic Hippocampi in Rats Cihan İŞLER, Taner TANRIVERDİ, Ersen KAVAK, Galip Zihni SANUS, Mustafa Onur ULU, Gözde ERKANLI, Ahmet KOMAN, Necla Birgül İYİSON, Mustafa UZAN Abstract ...
CNG-1 is a cyclic nucleotide-gated ion channel that is an essential component of the oxygen sensation pathway in URX (Busch et al. 2012; Couto et al. 2013). Thus, we hypothesized that perhaps egl-1 expression was driven by oxygen sensation and neuronal activity. We tested this hypothesis by quantifying reporter expression in other mutants defective in oxygen sensation, as well as in wild-type worms maintained in varying levels of environmental oxygen.. First, we quantified egl-1 reporter expression in mutants lacking gcy-35 or gcy-36. These genes encode soluble guanylyl-cyclases that heterodimerize and produce cGMP in response to binding molecular oxygen (Cheung et al. 2004). Both gcy-35 and gcy-36 are necessary for URX to respond to changes in environmental oxygen. We found that both gcy-35(ok769) and gcy-36(db42) loss-of-function mutants had a near complete lack of egl-1 reporter expression in URX (Figure 3B).. Prolonged calcium entry into URX through CNG-1 in response to long-term oxygen ...
The cone cyclic nucleotide-gated (CNG) channel is essential for central and color vision and for visual acuity. Mutations in the two channel subunits, CNGA3 and...
Cho, H-J., Staikopoulos, V., Furness, J.B., and Jennings, E.A. (2009) Inflammation-induced increase in hyperpolarization-activated, cyclic nucleotide-gated channel protein in trigeminal ganglion neurons and the effect of buprenorphine. Neuroscience, ...
1. Balague, C., Lin, B., Alcon, C., Flottes, G., and Malmstrom, S., et al. 2003. HLM1, an essential signaling component in the hypersensitive response, is a member of the cyclic nucleotide-gated channel ion channel family. Plant Cell 15:365-379.. 2. Barisic, K., Petrik, J., and Rumora, L. 2003. Biochemistry of apoptotic cell death. Acta Pharm. 53:151-164.. 3. Brodersen, P., Petersen, M., Pike, H. M., Olszak, B., and Skov, S., et al. 2002. Knockout of Arabidopsis accelerated-cell-death11 encoding a sphingosine transfer protein causes activation of programmed cell death and defense. Genes Dev. 16:490-502.. 4. Buckner, B., Johal, G. S., and Janick-Buckner, D. 2000. Cell death in maize. Physiol. Plant. 108:231-239.. 5. Buschges, R., Hollricher, K., Panstruga, R., Simons, G., and Wolter, M., et al. 1997. The barley Mlo gene: a novel control element of plant pathogen resistance. Cell 88:695-705.. 6. Cory, S., and Adams, J. M. 2002. The Bcl2 family: Regulators of the cellular life-or-death switch. Nat. ...
HCN3 antibody [S141-28] (hyperpolarization-activated, cyclic nucleotide-gated K+ 3) for ICC/IF, IHC, WB. Anti-HCN3 mAb (GTX41987) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] CNGA4 is a modulatory subunit of vertebrate cyclic nucleotide-gated membrane channels that transduce odorant signals (Munger et al., 2001 [PubMed 11739959]).[supplied by OMIM, Mar 2008 ...
Complete information for CNGA1 gene (Protein Coding), Cyclic Nucleotide Gated Channel Alpha 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CNGB3 gene (Protein Coding), Cyclic Nucleotide Gated Channel Beta 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are responsible for the functional hyperpolarization-activated current (I(h)) in dorsal root ganglion (DRG) neurons. We studied HCN1-4 channel mRNA and protein expression and correlated these findings with I(h) functional properties in rat DRG neurons of different size. Quantitative RT-PCR (TaqMan) analysis demonstrated that HCN2 and HCN1 mRNAs were more abundantly expressed in large diameter (55-80 microm) neurons, while HCN3 mRNA was preferentially expressed in small diameter (20-30 microm) neurons. HCN4 mRNA expression was very low in neurons of all sizes. At the protein level, subunit-selective polyclonal antibodies and immunofluorescence indicated that HCN1 and HCN3 are present in large diameter neurons and small diameter neurons. Staining in small diameter neurons was in IB4-positive (non-peptidergic) and IB4-negative (peptidergic) cells. HCN2 immunofluorescent staining was heterogeneous and predominantly in large diameter ...
Spinal cord injury (SCI) leads to bereft voluntary control of bladder, but the possible role of spontaneous excited system in bladder of SCI patients is poorly understood. Hyper-polarization-activated cyclic nucleotide-gated (HCN) channels are deemed to regulate the spontaneous contraction of bladder, our study explored the functional role of HCN channels in SCI induced neurogenic bladder. Sixty female Sprague-Dawley rats were randomized into control, sham and SCI groups. Rat models subjected to SCI at S2 levels were successfully established and were assessed using hematoxylin and eosin staining and cystometry. In SCI rats, the mRNA and protein expression levels of HCN channels and the Ih density were significantly reduced, and expression levels of several bladder HCN1 channel regulatory proteins were also significantly changed. The effects of 50 µM forskolin and 50 µM 8-bromoadenosine 3,5-cyclic monophosphate on [Ca2+]i of isolated bladder interstitial cells of Cajal-like cells were ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinsons disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive β oscillations, and alleviation of motor deficits in ...
The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinsons disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive β oscillations, and alleviation of motor deficits in ...
Moroni, A., Gorza, L., Beltrame, M., Gravante, B., Vaccari, T., Bianchi, M.E., Altomare, C., Longhi, R., Heurteaux, C., Vitadello, M., Malgaroli, A. and DiFrancesco, D. (2001) Hyperpolarization-activated cyclic nucleotide-gated channel 1 is a molecular determinant of the cardiac pacemaker current If. J. Biol. Chem., 276: 29233-29241 ...
Accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) upregulating its cell-surface expression and current density without affecting its voltage dependence and kinetics.
Hyperpolarization- and Cyclic Nucleotide-gated (HCN) channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. The HCN family consists of four members (HCN1-4). HCN channels represent the molecular correlates of I(h), a hyperpolarization-activated current best known for its role in controlling heart rate and in the regulation of neuronal resting membrane potential and excitability.. HCN channels are unique among vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization. HCN channels are encoded by four genes (HCN1-4) and are widely expressed throughout the heart and the central nervous system.. ...
Hyperpolarization-activated cyclic nucleotide-gated 1on channels (HCN) are gated by voltage, that is, they are able to detect changes in voltage and convert that into work for opening and closing (gating) the channel gate. The focus of this thesis was to investigate the gating mechanisms in HCN channels. Results from these experiments revealed that HCN channels have a voltage sensor (S4) similar to K v channels but have reversed gating. This makes up the first half of the thesis. In addition, the outward currents through HCN channels are susceptible to a voltage-dependent block by intracellular Mg2+. The experiments relating to the Mg2+ block make up the second half of the thesis. HCN channels mediate an inward cation current that contributes to spontaneous rhythmic firing activity in the heart and brain. These channels share homology with depolarization-activated Kv channels, including six transmembrane domains (S 1-S6) and a positively charged S4 segment. The S4 domain has been shown to function as
It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories. cAMP has three targets, protein kinase A (PKA), hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels, and exchange protein activated by cAMP (Epac). Studies have revealed that both PKA and HCN channels are important for long-term memory formation. However, little is known about the role of Epac in this process. Epac is a cAMP- dependent guanine nucleotide exchange factor for the small G proteins including Rap1.The Epac2 isoform is highly expressed in the forebrain. This dissertation examines the role of Epac in memory formation in several aspects. First, I show that activation of Epac within the hippocampus via intrahippocampal injection of Epac specific agonist 8-pCPT-2-O-Me-cAMP was able to enhance long-term memory formation in a PKA independent fashion. Next, I show that the levels of Rap1 activity, the direct target of Epac, increased during the memory formation.
KCNH channels are voltage-gated potassium channels with important physiological functions. In these channels, a C-terminal cytoplasmic region, known as the cyclic nucleotide binding homology (CNB-homology) domain displays strong sequence similarity to cyclic nucleotide binding (CNB) domains. However, the isolated domain does not bind cyclic nucleotides. Here, we report the X-ray structure of the CNB-homology domain from the mouse EAG1 channel. Through comparison with the recently determined structure of the CNB-homology domain from the zebrafish ELK (eag-like K(+)) channel and the CNB domains from the MlotiK1 and HCN (hyperpolarization-activated cyclic nucleotide-gated) potassium channels, we establish the structural features of CNB-homology domains that explain the low affinity for cyclic nucleotides. Our structure establishes that the self-liganded conformation, where two residues of the C-terminus of the domain are bound in an equivalent position to cyclic nucleotides in CNB domains, is a conserved
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated potassium ion channels. They are, however, activated by hyperpolarizing potentials and are permeable to cations. Four HCN subunits have been cloned, of which HCN1 and HCN2 subunits are p …
2Institute of Neuroscience, National Research Council, Cagliari, Italy. It is widely accepted that ligand-gated and voltage-dependent ion channels are crucial in mediating many of the central pharmacological and behavioral actions of ethanol (EtOH). Recent studies reported that the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels expressed in VTA neurons as well as hippocampal interneurons are modulated by EtOH, suggesting that they may represent an additional sensitive target for this drug. HCN channels are encoded by four HCN genes (HCN1-4), and their activation generates a typical inward current, termed Ih, which plays an important role in controlling neuronal resting membrane potential and firing rate of action potentials, and are heavily implicated in dendritic integration of post-synaptic potentials. Since HCN are highly expressed in CA3 glutamatergic pyramidal neurons, we have investigated the action of EtOH on Ih in these hippocampal cells from ...
Similar experiments were performed with cDNA derived from poly(A)+ RNA of bovine pineal tissue. Two overlapping fragments, harboring either the 5′ or 3′ part of the coding region for rod and cone CNG channels were amplified by two sets of primers similar to those used for amplification of fragments from chick cDNA.. Analysis of genomic structure of chick cone CNG channel. A chick genomic library in λFIXII-vector (Stratagene, La Jolla, Ca) was screened with two cDNA probes (F5′, nucleotides −39 to 926, and F3′, nucleotides 882 to 2391 of pCCG8B; Bönigk et al., 1993). Probe F5′ and F3′ yielded 12 and 7 positive signals, respectively. Two overlapping clones were chosen for further analysis. Clones were digested with SacI, XbaI, EcoRI,BamHI, SalI, and each possible combination of two endonucleases. Fragments were separated by agarose electrophoresis and those containing exon sequences were identified by Southern blotting using probes F5′ and F3′. These fragments were isolated and ...
In situ hybridization studies of mouse brain have revealed distinct but overlapping patterns of expression of HCN1 and HCN2 (Moosmang et al. 1999; Monteggia et al. 2000; Santoro et al. 2000). Single cell PCR studies provide additional strong evidence for coexpression of different HCN isoforms within single neurons (Franz et al. 2000). In particular, both HCN1 and HCN2 are prominently expressed in CA3 and CA1 pyramidal neurons of the hippocampus. Whole-cell patch-clamp recordings demonstrate a prominent Ih current with relatively rapid kinetics in CA1 pyramidal neurons. The presence of multiple HCN isoforms in a given cell raises the question as to whether the Ih current in these cells results from separate populations of homomeric channels or whether the different isoforms coassemble to form heteromultimeric channels.. By coexpressing HCN1 and HCN2 in Xenopus oocytes, we have provided several lines of functional evidence that the two isoforms can indeed coassemble to form functional ...
ID CN15C_MEDTR Reviewed; 703 AA. AC A0A072VMJ3; DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2014, sequence version 1. DT 25-OCT-2017, entry version 20. DE RecName: Full=Protein CNGC15c {ECO:0000303,PubMed:27230377}; DE AltName: Full=Cyclic nucleotide-gated ion channel protein 15 c {ECO:0000303,PubMed:27230377}; GN Name=CNGC15C {ECO:0000303,PubMed:27230377}; GN OrderedLocusNames=MTR_2g094860 {ECO:0000312,EnsemblPlants:KEH39345}; OS Medicago truncatula (Barrel medic) (Medicago tribuloides). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae; OC Pentapetalae; rosids; fabids; Fabales; Fabaceae; Papilionoideae; OC Trifolieae; Medicago. OX NCBI_TaxID=3880 {ECO:0000312,Proteomes:UP000002051}; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Jemalong A17; RX PubMed=22089132; DOI=10.1038/nature10625; RA Young N.D., Debelle F., Oldroyd G.E.D., Geurts R., Cannon S.B., RA Udvardi M.K., ...
ID A0A151R9I9_CAJCA Unreviewed; 418 AA. AC A0A151R9I9; DT 08-JUN-2016, integrated into UniProtKB/TrEMBL. DT 08-JUN-2016, sequence version 1. DT 25-OCT-2017, entry version 7. DE SubName: Full=Putative cyclic nucleotide-gated ion channel 19 {ECO:0000313,EMBL:KYP39025.1}; DE Flags: Fragment; GN ORFNames=KK1_039698 {ECO:0000313,EMBL:KYP39025.1}; OS Cajanus cajan (Pigeon pea) (Cajanus indicus). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae; OC Pentapetalae; rosids; fabids; Fabales; Fabaceae; Papilionoideae; OC Phaseoleae; Cajanus. OX NCBI_TaxID=3821 {ECO:0000313,EMBL:KYP39025.1, ECO:0000313,Proteomes:UP000075243}; RN [1] {ECO:0000313,EMBL:KYP39025.1, ECO:0000313,Proteomes:UP000075243} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Asha {ECO:0000313,Proteomes:UP000075243}; RX PubMed=22057054; DOI=10.1038/nbt.2022; RA Varshney R.K., Chen W., Li Y., Bharti A.K., Saxena R.K., RA Schlueter J.A., Donoghue ...
Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule cells (GCs) in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation. Using whole-cell recording in rat hippocampal slices, we investigated the net LTG effect on BC output. We showed that bath application of LTG significantly decreased the amplitude of evoked compound inhibitory postsynaptic currents (IPSCs) in GCs. In contrast, simultaneous paired recordings from BCs to GCs showed that LTG had no effect on both the amplitude and the paired-pulse ratio of the unitary IPSCs, suggesting that LTG did not
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A chronic compression of the DRG (CCD) produces cutaneous hyperalgesia and an enhanced excitability of neuronal somata in the compressed ganglion. The hyperpolarization-activated current (I(h)), present in the somata and axons of DRG neurons, acts to induce a depolarization after a hyperpolarizing event and, if upregulated after CCD, may contribute to enhanced neuronal excitability. Whole-cell patch-clamp recordings were obtained from acutely dissociated, retrogradely labeled, cutaneous, adult rat DRG neurons of medium size. Neurons were dissociated from L4 and L5 control DRGs or DRGs that had each been compressed for 5-7 d by L-shaped rods inserted into the intervertebral foramina. I(h), consisting of a slowly activating inward current during a step hyperpolarization, was recorded from every labeled, medium-sized neuron and was blocked by 1 mm cesium or 15 microm ZD7288. Compared with control, CCD increased the current density and rate of activation significantly without changing its reversal ...
HCN1 antibody [S70-28] (hyperpolarization-activated cyclic nucleotide-gated potassium channel 1) for IHC, IHC-Fr, IP, WB. Anti-HCN1 mAb (GTX41985) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
The backprojected volume was obtained from image processing of 2D crystal images of the potassium channel MloK1, via a novel software suite implemented in the 2dx and FOCUS software packages (http://focus-em.org). The PCO refined volume was obtained by applying projective constraint optimization to the backprojected volume.
CNGB1 Full-Length MS Protein Standard (NP_001129111), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene.
Neuropathic pain is induced by the injury to nervous systems and characterized by hyperalgesia, allodynia and spontaneous pain. The underlying mechanisms include peripheral and central sensitization resulted from neuronal hyperexcitability. A number of ion channels are considered to contribute to the neuronal hyperexcitability. Here, we particularly concentrate on an interesting ion channel, hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We overview its biophysical properties, physiological functions, followed by focusing on the current progress in the study of its role in the development of neuropathic pain. We attempt to provide a comprehensive review of the potential valuable target, HCN channels, in the treatment of neuropathic pain. ...
Hyperpolarization-activated cAMP-regulated (HCN) channels play important physiological roles in both cardiovascular and central nervous systems. Among the four HCN isoforms, HCN2 and HCN4 show high expression levels in the human heart, with HCN4 being the major cardiac isoform. Previously published crystal structure of mouse HCN2 (mHCN2) C-terminal fragment, including the C-linker and the cyclic-nucleotide binding domain (CNBD), has provided many insights into the cAMP-dependent gating in HCN channels. However, structures of other mammalian HCN channel isoforms have been lacking. Here we used a combination of approaches including structural biology, biochemistry, and electrophysiology, to study the cAMP-dependent gating in HCN4 channels. First we solved the crystal structure of the C-terminal fragment of human HCN4 (hHCN4) channel at 2.4A. Overall we observed a high similarity between mHCN2 and hHCN4 crystal structures. Functional comparison between two isoforms revealed that compared to mHCN2, ...
COMMENT Ih current - hyperpolarization-activated nonspecific Na and K channel - contributes to the resting membrane potential - controls the afterhyperpolarization Reference: 1. Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130, 1996. V1/2 = -84.1 mV k = 10.2 reversal potential = -32.9 +/- 1.1 mV at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms t2 = 1.04+/-0.16 s 2. Maccaferri, G. et al. Properties of the Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993. V1/2 = -97.9 mV k = 13.4 reversal potential = -18.3 mV 3. Pape, H.C. Queer current and pacemaker: The hyperpolarization-activated cation current in neurons, Annu. Rev. Physiol. 58:299-327, 1996. single channel conductance is around ...
COMMENT Ih current - hyperpolarization-activated nonspecific Na and K channel - contributes to the resting membrane potential - controls the afterhyperpolarization Reference: 1. Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130, 1996. V1/2 = -84.1 mV k = 10.2 reversal potential = -32.9 +/- 1.1 mV at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms t2 = 1.04+/-0.16 s 2. Maccaferri, G. et al. Properties of the Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993. V1/2 = -97.9 mV k = 13.4 reversal potential = -18.3 mV 3. Pape, H.C. Queer current and pacemaker: The hyperpolarization-activated cation current in neurons, Annu. Rev. Physiol. 58:299-327, 1996. single channel conductance is around ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Function of the hyperpolarization-activated inward rectification in nonmyelinated peripheral rat and human axons.: The function of time-dependent, hyperpolariza
The membrane protein encoded by this gene is a hyperpolarization-activated cation channel that contributes to the native pacemaker currents in heart and neurons. The encoded protein can homodimerize or heterodimerize with other pore-forming subunits to form a potassium channel. This channel may act as a receptor for sour tastes. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments ...
Gabapentin (GBP) is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2 and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+) or calretinin positive (CR+) inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100µM) caused a hyperpolarizing shift in the voltage of half activation (V1/2) thereby reducing the currents. GBP had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1
Like CNG channels, the HCN cation channels are members of the six-transmembrane superfamily (Kaupp and Seifert, 2001; Biel et al., 2002; Robinson and Siegelbaum, 2003). In contrast to most other voltage-gated channels, HCN channels open upon hyperpolarization and close at positive potential. The cyclic nucleotides cAMP and cGMP enhance HCN channel activity by shifting the activation curve of the channels to more positive voltages. The stimulatory effect of cyclic nucleotides does not depend on protein phosphorylation but is caused by direct interaction with the HCN channel protein. The current produced by HCN channels, termed Ih, If, or Iq, is found in a variety of excitable cells, including neurones, cardiac pacemaker cells, and photoreceptors (Pape, 1996; Robinson and Siegelbaum, 2003). The best-understood function of Ih is to control heart rate and rhythm by acting as pacemaker current in the sinoatrial (SA) node (Stieber et al., 2004). Ih is activated during the membrane hyperpolarization ...
Zatebradine Zatebradine(UL-FS49) is a potent HCN channels antagonist, which decreased the heartbeat in a reversible manner; 92% inhibition of the hHCN1-mediated current at 10 uM. ...
Cyclic nucleotide-gated cation channel alpha-3 Description. Visual signal transduction is mediated by a G-protein coupled ... This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a ... Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased ... sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3 (By similarity). ...
Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: ...
Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: ...
Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: ...
Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: ...
Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: ...
... a constitutively active gpcr as a driving force for camp production gold coast and a cyclic nucleotide gated cng cation channel ... Ary news is latino senior dating online site a complete news channel which covers every element of the news including sport. ...
... cyclic nucleotide-gated ion channel activity[*], voltage-gated ion channel activity[*], G-protein gated ion channel activity[*] ... In physica e chimia un ion es un atomo o molecula con carga electric.Si le carga electric esse positiva illo es nominate cation ... ATP-gated ion channel activity[*], ATPase-coupled ion transmembrane transporter activity[*], ...
... is a family of transient receptor potential ion channels where the M stands for melastatin.[1] Functional TRPM ... Voltage-gated ion channel • Ligand-gated ion channelCyclic nucleotide-gated ion channel (α1, α3, β3, H1, H2, H4) • Stretch- ... Cation channels of sperm • Two-pore channel. Na+: Sodium channel. Navα (1.1, 1.2, 1.4, 1.5, 1.7, 1.9) • Navβ (1, 3, 4) • ... Membrane transport protein: ion channels. Ca2+: Calcium channel. Voltage-dependent calcium channel (L-type/Cavα(1.1, 1.2, 1.3, ...
Regulation Of Acid-sensing Ion Channel Activity. *Regulation Of Cation Channel Activity ... Positive Regulation Of Cyclic-nucleotide Phosphodiesterase Activity. *Response To Abiotic Stimulus. *Positive Regulation Of ... Regulation Of High Voltage-gated Calcium Channel Activity. *Regulation Of Ion Transmembrane Transporter Activity ... Positive Regulation Of Ryanodine-sensitive Calcium-release Channel Activity. *Positive Regulation Of Intrinsic Apoptotic ...
Positive Regulation Of Cyclic-nucleotide Phosphodiesterase Activity. *Positive Regulation Of Anoikis. *Regulation Of High ... Negative Regulation Of Cation Channel Activity. *Polysaccharide Catabolic Process. *Positive Regulation Of Monooxygenase ... Regulation Of Voltage-gated Calcium Channel Activity. *Positive Regulation Of Protein Dephosphorylation ...
Regulation Of High Voltage-gated Calcium Channel Activity. *Regulation Of Cell Communication By Electrical Coupling Involved In ... Positive Regulation Of Cyclic-nucleotide Phosphodiesterase Activity. *DNA Methylation On Cytosine Within A CG Sequence ... Negative Regulation Of Cation Channel Activity. *Regulation Of DNA Methylation. *Polysaccharide Catabolic Process ... Negative Regulation Of Ryanodine-sensitive Calcium-release Channel Activity. *Positive Regulation Of Ryanodine-sensitive ...
Regulation Of High Voltage-gated Calcium Channel Activity. *Regulation Of Cell Communication By Electrical Coupling Involved In ... Positive Regulation Of Cyclic Nucleotide Metabolic Process. *Positive Regulation Of Protein Autophosphorylation ... Cation Transmembrane Transport. *Transmembrane Transport. *Regulation Of Adrenergic Receptor Signaling Pathway. *Regulation Of ... Negative Regulation Of Ryanodine-sensitive Calcium-release Channel Activity. *Positive Regulation Of Ryanodine-sensitive ...
Regulation Of Voltage-gated Calcium Channel Activity. *Negative Regulation Of Cation Channel Activity ... Positive Regulation Of Cyclic Nucleotide Metabolic Process. *Positive Regulation Of Protein Autophosphorylation ... Regulation Of High Voltage-gated Calcium Channel Activity. *Positive Regulation Of Ryanodine-sensitive Calcium-release Channel ... Regulation Of High Voltage-gated Calcium Channel Activity. *Regulation Of Cell Communication By Electrical Coupling Involved In ...
CSPN)(FPGA)(SDDO)BlockControlledDataDependentFieldHybridOperationSwitchablearrayciphergatemodelnetworkspermutationprogrammable ... antigenicbinding,cchemistry,corecrystal-structure,dependentderivatives,discovery,dqcauchilehcvhepatitisns5bnucleosidenucleotide ... 1Cation-Dependent Light-Induced Halide Demixing in Hybrid Organic-Inorganic Perovskites. ...
  • Subunit of cyclic nucleotide-gated (CNG) channels, nonselective cation channels, which play important roles in both visual and olfactory signal transduction. (uniprot.org)
  • RT-PCR data suggest that mRNA of both αCNC1 and βCNC subunits are present in A549 cells and the presence of the βCNC subunit, may as previously reported, increase the affinity of these channel blockers compared to the hαCNC1 subunit alone. (elsevier.com)
  • 1989) of what is now known to be the CNG channel α subunit facilitated its molecular characterization. (ubc.ca)
  • Expression in mammalian cells helped resolve confusion regarding the JVL of the rod CNG channel a subunit. (ubc.ca)
  • PCR was used to construct cDNA clones which code for both the 63 and 80 kDa forms of the a subunit of the rod CNG channel. (ubc.ca)
  • The cloned CNG channel β subunit cDNA codes for a protein with a predicted molecular mass of 155 kDa (Korschen et al, 1995). (ubc.ca)
  • The expressed a subunit reconstituted alone did not generate functional cGMP-gated channels. (ubc.ca)
  • The system presented here will be useful to further define CNG α and β subunit interactions and to carry out structure-function studies on the channel using a biochemical efflux assay. (ubc.ca)
  • 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)
  • This paper describes the characterization of CNCβ1b, a third subunit expressed in OSNs and establishes it as a component of the native channel. (jneurosci.org)
  • Thus, CNG channels in both rod photoreceptors and olfactory sensory neurons result from coassembly of specific α subunits with various forms of an alternatively spliced β subunit. (jneurosci.org)
  • Rod and cone photoreceptors, as well as OSNs, each express a specific principal subunit, commonly referred to as α subunit, which is responsible for many of the key channel characteristics. (jneurosci.org)
  • photoreceptor cGMP-gated channel α-subunit. (tcdb.org)
  • 1] "Cloning, chromosomal localization and functional expression of the gene encoding the alpha-subunit of the cGMP-gated channel in human cone photoreceptors. (tcdb.org)
  • 6] "Subunit configuration of heteromeric cone cyclic nucleotide-gated channels. (tcdb.org)
  • 7] "Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. (tcdb.org)
  • 10] "Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit. (tcdb.org)
  • These alterations were due to decreased I(h) availability, via a decline in HCN1/HCN2 subunit expression resulting in decreased h currents, and altered kinetics of the residual channels. (nih.gov)
  • By PCR analysis and cloning of the respective cDNA, we show that the chick pineal expresses the α-subunit of the cyclic nucleotide-gated (CNG) channel of rod photoreceptors and two short forms of the cone CNG channel. (jneurosci.org)
  • This exon is missing in the gene for the rod CNG channel α-subunit. (jneurosci.org)
  • Achromatopsia type 2 (ACHM2) is a severe, inherited eye disease caused by mutations in the CNGA3 gene encoding the α subunit of the cone photoreceptor cyclic nucleotide-gated (CNG) channel. (frontiersin.org)
  • This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. (genecards.org)
  • This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. (genscript.com)
  • The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. (genscript.com)
  • Cyclic nucleotide-gated channel subunit glycosylation regulates matrix metalloproteinase-dependent changes in channel gating. (genscript.com)
  • Subunit stoichiometry of CNG channels in photoreceptors and olfactory neurons. (els.net)
  • Similarly to voltage‐gated K + channels, CNG channels are tetramers where each subunit contains six transmembrane domains, intracellular N ‐ and C ‐termini, positive charges in the fourth transmembrane domain (S4), and a P‐loop lining the pore of the channel. (els.net)
  • In addition, CNG channels contain a cyclic nucleotide‐binding domain in the C ‐terminus of each subunit, connected to the transmembrane domain by a region called the C‐linker. (els.net)
  • b) Structure of the cytoplasmic domain from a single subunit of HCN2 channels (PDB: 1Q5O). (els.net)
  • A) Topology of the CNG channel subunit, highlighting the BD region substituted in the X-chimera series of constructs. (nih.gov)
  • Knockout of GARPs and the β-subunit of the rod cGMP-gated channel disrupts disk morphogenesis and rod outer segment structural integrity. (nih.gov)
  • this channel consists of two subunit types, alpha and beta. (nih.gov)
  • In the rod cells, the Cngb1 locus encodes the channel beta-subunit and two related glutamic-acid-rich proteins (GARPs). (nih.gov)
  • Additionally, a marked reduction in the level of channel alpha-subunit, guanylate cyclase I (GC1) and ATP-binding cassette transporter (ABCA4) was observed without affecting levels of other ROS proteins, consistent with a requirement for the beta-subunit in channel assembly or targeting of select proteins to ROS. (nih.gov)
  • Remarkably, phototransduction still occurred when only trace levels of homomeric alpha-subunit channels were present, although rod sensitivity and response amplitude were both substantially reduced. (nih.gov)
  • The HCN2 gene encodes the pore-forming subunit of a hyperpolarization-gated, cyclic nucleotide-sensitive, non-selective cation channel. (criver.com)
  • The human HCN4 gene encodes the pore-forming subunit of a hyperpolarization-activated, cyclic nucleotide-modulated cation channel. (creativebiomart.net)
  • Truncation of TRPV1, expression of cytosolic termini of TRPV1 or TRPV4 and construction of chimeric TRPV channel subunits revealed that the specificity and the affinity of the subunit interaction is synergistically provided by interaction modules located in the transmembrane domains and in the cytosolic termini. (biologists.org)
  • The subunit composition may influence the biophysical and regulatory properties of the resulting channel complex. (biologists.org)
  • p>This subsection of the 'Function' section describes a region in the protein which binds nucleotide phosphates. (uniprot.org)
  • This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a depolarization of cone photoreceptors. (uniprot.org)
  • This protection effect did not occur in intact cells and was probably a consequence of patch excision, possibly representing ablation of a regulatory protein from the channel cyclic nucleotide binding site. (rupress.org)
  • Thus, the binding of divalent cations, probably via a regulatory protein, controls the sensitivity of the cAMP-gated channels to cAMP. (rupress.org)
  • CNGA3 [600053], protein: cyclic nucleotide-gated cation channel, α3. (nature.com)
  • CNGB3 [605080], protein: cyclic nucleotide-gated cation channel, β3. (nature.com)
  • GNAT2 [139340], protein: guanine nucleotide-binding protein, α-transducing activity polypeptide 2. (nature.com)
  • Because of their substantial Ca 2+ permeability (for review, see Kaupp, 1995 ), CNG channels may be utilized by G-protein-coupled receptor pathways to control [Ca 2+ ] i in pinealocytes through changes in the concentration of cAMP and cGMP. (jneurosci.org)
  • CNGB1 (Cyclic Nucleotide Gated Channel Beta 1) is a Protein Coding gene. (genecards.org)
  • The protein exhibits all essential properties of an I h -channel. (tum.de)
  • Along with another protein, the encoded protein forms a cGMP-gated cation channel in the plasma membrane, allowing depolarization of rod photoreceptors. (genecards.org)
  • Cyclic nucleotide gated channel alpha 2, also known as CNGA2, is a human gene encoding an ion channel protein. (wikipedia.org)
  • 6 Like NO, cGMP can affect multiple signaling pathways ( Figure 1 A). 1,5,6 To date, three classes of cGMP receptor proteins have been identified: cyclic nucleotide-gated (CNG) cation channels, cGMP-regulated PDEs, which hydrolyze cAMP and/or cGMP, and cGMP-dependent protein kinases (cGKs). (ahajournals.org)
  • HCN4 channel protein expression and phosphorylation were measured by immunoblotting and fluorescent quantitation. (hindawi.com)
  • Here, we further investigated HCN4 channel protein expression and phosphorylation to explore the mechanisms involved in the treatment effects of Yiqi Tongyang for SSS. (hindawi.com)
  • Most of these mutations change single protein building blocks (amino acids) in the HCN4 channel. (medlineplus.gov)
  • These results support the notion that the selectivity filter of the channel must be properly anchored to the surrounding protein structure in order for CNGA1 channels to achieve their physiological role. (upenn.edu)
  • The cGMP sensitivity of cyclic nucleotide-gated (CNG) channels can be modulated by changes in phosphorylation catalyzed by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases. (rupress.org)
  • Similar complexes between ion channels, protein kinases, and protein phosphatases have been shown for several other channels ( Levitan 1999 ) and may be the rule rather than the exception. (rupress.org)
  • Aiba, H. , Fujimoto, S. , Ozaki, N. 1982 Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP receptor protein. (wiley.com)
  • Genetic truncation of the transmembrane disintegrin and metalloproteinase protein ADAM11 resulted in the absence of Kv1 channels that are normally densely clustered at the terminals of basket cell axons in the cerebellar cortex. (jneurosci.org)
  • Catabolite gene activator protein (CAP) is a prokaryotic homologue of eukaryotic cNMP-binding domains, present in ion channels, and cNMP-dependent kinases. (embl.de)
  • cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. (embl.de)
  • One is crystallographic, aimed at determining the structure of the closed and opened form of the channel, and the other electrophysiologic, studying the effects of mutations in the Ca 2+ -binding site, the channel's inner helices that line the pore, and in the intervening protein. (utsouthwestern.edu)
  • Signaling through the cyclic adenosine monophosphate-dependent protein kinase [protein kinase A (PKA)] is an important and widely studied area of signal transduction research. (sciencemag.org)
  • Various stimuli activate adenylyl cyclase, but the best studied is ligand occupation of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) coupled to G s . (sciencemag.org)
  • cAMP has three direct intracellular targets: protein kinase A (PKA), the exchange protein activated by cAMP (Epac), and cyclic nucleotide-gated ion channels (CNGCs). (sciencemag.org)
  • Epac is a guanine nucleotide exchange factor for the small G protein Rap1 and has been implicated in a number of cellular processes such as insulin secretion, neurotransmitter release, and integrin-mediated cell adhesion ( 4 - 6 ). (sciencemag.org)
  • With an understanding of the protein domains which can bind cyclic nucleotides (CNB and GAF domains) we scanned the completed genomes of the higher plants Arabidopsis thaliana (mustard weed) and Oryza sativa (rice) for the effectors of these signalling molecules. (biomedcentral.com)
  • Contrary to some reports, we found no biochemical or bioinformatic evidence for a plant cyclic nucleotide regulated protein kinase, suggesting that cyclic nucleotide functions in plants have evolved differently than in mammals. (biomedcentral.com)
  • Cyclic nucleotides are able to bind to two distinct protein domains, CNB domains and GAF domains. (biomedcentral.com)
  • This gene encodes a multi-pass membrane protein that functions as a voltage gated cation channel. (genetex.com)
  • The encoded protein is a member of a family of closely related cyclic adenosine monophosphate-binding channel proteins. (genetex.com)
  • All of these physiological processes are mediated in part by members of the voltage-gated ion channel protein superfamily ( Fig. 1 ) ( Yu and Catterall, 2004 ). (aspetjournals.org)
  • The inwardly rectifying potassium channels comprise the simplest structural motif in the ion channel protein superfamily. (aspetjournals.org)
  • CNGCs, nonselective cation channels that open upon cyclic nucleotide binding, are particularly important in the olfactory and visual systems ( 3 ). (sciencemag.org)
  • Anderson, J.A. , Huprikar, S.S. , Kochian, L.V. , Lucas, W.J. , Gaber, R.F. 1992 Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae . (wiley.com)
  • Köhler, C. & Neuhaus, G. 1998 Cloning and partial characterization of two putative cyclic nucleotide-regulated ion channels from Arabidopsis thaliana , designated CNGC1 (Y16327) and CNGC, 2 (Y 16328). (wiley.com)
  • 2007) Death don't have no mercy and neither does calcium: Arabidopsis cyclic nucleotide gated channel2 and innate immunity. (els.net)
  • See commentary " Calmodulin binding to Arabidopsis cyclic nucleotide gated ion channels " in Plant Signal Behav , volume 5 on page 1147. (pubmedcentralcanada.ca)
  • In order to further explore the roles of cyclic nucleotides in plants, we performed a bioinformatics based analysis of the completed Arabidopsis thaliana and Orzya sativa genomes [ 21 - 23 ] in order to elucidate the potential targets of cyclic nucleotides in plants. (biomedcentral.com)
  • 4] "Phylogenetic relationships within cation transporter families of Arabidopsis. (tcdb.org)
  • Hyperpolarization activated cyclic nucleotide-gated cation (HCN) channels are involved in neuronal rhythm regulation , synaptic activity, membrane resistance and dendritic integration due to their voltage-gated physiological properties. (bvsalud.org)
  • In der vorliegenden Arbeit wurde eine cDNA charakterisiert, die für den "murine hyperpolarization-activated cyclic nucleotide-gated cation channel 1" (mHCN1) codiert. (tum.de)
  • Here a cDNA was identified which codes for the "murine hyperpolarization-activated cyclic nucleotide-gated cation channel 1" (mHCN1). (tum.de)
  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a family of cation channels activated by hyperpolarized membrane potentials and stimulated by intracellular cyclic nucleotides. (mdpi.com)
  • The ion channel family of hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels comprises four members termed HCN1-4. (mdpi.com)
  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. (nih.gov)
  • The family of cyclic nucleotide-regulated channels comprises two groups: the cyclic nucleotide-gated (CNG 1 ) channels and the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. (aspetjournals.org)
  • In this study, we report that the PKC inhibitors induce a prolonged Ca 2+ import through hyperpolarization‐activated cyclic nucleotide‐gated channel 2 (HCN2) in lung carcinoma cells and in primary culture of cortical neurons, sufficient to trigger apoptosis‐inducing factor (AIF)‐mediated apoptosis. (embopress.org)
  • I f is carried by the hyperpolarization-activated cyclic nucleotide-gated ion channels (Hcn1-4), members of the voltage-gated ion channel superfamily ( 12 ). (onlinejacc.org)
  • Hyperpolarization-activated Cyclic Nucleotide-gated, HCN, channels contribute to the membrane potential of excitable cells including pacemaker cells of the heart and neurons in the brain. (ubc.ca)
  • HEK293-HuHCN4 cell line is a hypotriploid human cell line, which has been transfected with a human hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4), to allow stably express of the human HCN4. (creativebiomart.net)
  • Dynamic Expression of Hyperpolarization-activated Cyclic Nucleotide-gated Cation Channel 4 Involved in Microwave Induced Pacemaker Cell Injuries. (emf-portal.org)
  • The CNGA3 channel is primarily expressed in cone photoreceptors where it participates in light transduction (daylight and color vision). (biomol.com)
  • 12] "Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia. (tcdb.org)
  • The native CNG channels are composed of alpha and beta subunits in a tetrameric configuration. (biomol.com)
  • 5In a heterologous expression system, only the alpha subunits are capable of forming functional homomeric channels. (biomol.com)
  • A heterologous expression system was developed to examine molecular aspects of the α and β subunits of the CNG channel. (ubc.ca)
  • As seen for the subunits of the native CNG channel the heterologously expressed α and β subunits coimmunoprecipitated. (ubc.ca)
  • Reconstitution of the heterologously expressed channel complex comprising the 80 kDa α and complete β subunits generated functional channels. (ubc.ca)
  • Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. (ebi.ac.uk)
  • From single-channel analyses of native rat olfactory channels and of channels expressed heterologously from all possible combinations of the CNCα3, -α4, and -β1b subunits, we conclude that the native CNG channel in OSNs is composed of all three subunits. (jneurosci.org)
  • suggest that the native rod channel is built exclusively from these two subunits. (jneurosci.org)
  • For simplicity, this figure shows two of the four subunits comprising CNG channels. (els.net)
  • Previously, we used genistein, a PTK inhibitor, to probe the interaction between PTKs and homomeric channels comprised of α subunits (RETα) of rod photoreceptor CNG channels expressed in Xenopus oocytes. (rupress.org)
  • Native CNG channels are heteromers, containing β as well as α subunits. (rupress.org)
  • To determine the contributions of α and β subunits to genistein inhibition, we compared the effect of genistein on native, homomeric (RETα and OLFα), and heteromeric (RETα+β, OLFα+β, and OLFα+RETβ) CNG channels. (rupress.org)
  • We found that genistein only inhibits channels that contain either the RETα or the OLFβ subunits. (rupress.org)
  • Exogenous expression of α subunits alone generates functional CNG channels in oocytes. (rupress.org)
  • In contrast, β subunits do not form functional channels when expressed alone. (rupress.org)
  • Both types of subunits are members of the six-transmembrane segment channel superfamily. (aspetjournals.org)
  • In the cytosolic C terminus, CNG channel subunits carry a cyclic nucleotide-binding domain (CNBD) that serves as activation domain. (aspetjournals.org)
  • HCN channels consist of four subunits that have six transmembrane segments [ 4 ], the canonical GYG sequence in the pore forming region, and the positively charged S4 segment [ 4 , 5 ]. (hindawi.com)
  • As the specificity of TRPV channel heteromerization and determinants governing the assembly of TRPV subunits were largely elusive, we investigated the TRPV homo- and heteromultimerization. (biologists.org)
  • To analyze the assembly of TRPV subunits in living cells, we generated fluorescent fusion proteins or FLAG-tagged TRPV channel subunits. (biologists.org)
  • Our results demonstrate that TRPV channel subunits do not combine arbitrarily. (biologists.org)
  • With the exception of TRPV5 and TRPV6, TRPV channel subunits preferentially assemble into homomeric complexes. (biologists.org)
  • Robinson and Siegelbaum, 2003 ), TRP channel subunits presumably assemble into homo- or heterotetrameric channel complexes. (biologists.org)
  • We studied the selectivity and promiscuity of homo- and heteromultimerization between TRPV channel subunits in living cells. (biologists.org)
  • The α subunits have an overall structural resemblance to those of the sodium channels and are equally large. (wikidoc.org)
  • The α subunits have six transmembrane segments, homologous to a single domain of the sodium channels. (wikidoc.org)
  • Our findings demonstrate a novel role for the HCN2 channel by providing evidence that it can act as an upstream regulator of cell death triggered by PKC inhibitors. (embopress.org)
  • HCN2 channels expressed in the heart contribute to the pacemaker current (Ih). (criver.com)
  • Finally, we elucidated the mechanism behind two disease-associated mutations found in the cytosolic C-linker/binding domain portion of the HCN2 and HCN4 channels to gain a better understanding of how they influence cAMP binding and channel opening, and cause epilepsy and profound bradycardia, respectively. (ubc.ca)
  • Ion channels that are regulated by cyclic GMP or cyclic AMP binding and contain six transmembrane segments and an ion conducting pore that passes monovalent cations. (harvard.edu)
  • HCN channels belong to the superfamily of voltage-gated pore loop channels. (ebi.ac.uk)
  • HCN channels contain six membrane-spanning helices (S1-S6), including a positively charged voltage-sensing S4 segment and an ion-conducting pore between S5 and S6. (ebi.ac.uk)
  • That is, affinity of blocking agents for the pore of ion channels varies with membrane voltage. (upenn.edu)
  • Eismann, E. , Muller, F. , Heinemann, S.H. , Kaupp, U.B. 1994 A single negative charge within the pore region of a cGMP-gated channel controls rectification, Ca 2+ blockage, and ionic selectivity. (wiley.com)
  • There are two fundamental properties of ion channels: ion selectivity and gating of the pore. (utsouthwestern.edu)
  • In virtually every ligand-gated tetrameric cation channel, amino acid sequence analysis reveals the presence of a ligand-binding domain located on the C-terminal side of the pore. (utsouthwestern.edu)
  • The structure of CNGCs is similar to that of the voltage-gated outward rectifying K + -selective ion channel (Shaker) proteins, including a cytoplasmic N-terminus, six membrane spanning regions (S1-S6), a pore domain located between S5 and S6, and a cytoplasmic C-terminus ( Zagotta and Siegelbaum, 1996 ). (pubmedcentralcanada.ca)
  • We also found that two partial agonists, cCMP and cIMP, bound to the canonical site, but failed to fully promote tetrameric gating ring which is found on the inner side of the pore and hypothesized to facilitate its opening. (ubc.ca)
  • Ion channels are pore-forming proteins that help to establish and control the small voltage gradient across the plasma membrane of all living cells (see cell potential ) by allowing the flow of ions down their electrochemical gradient . (wikidoc.org)
  • While some channels permit the passage of ions based solely on charge, the archetypal channel pore is just one or two atoms wide at its narrowest point. (wikidoc.org)
  • In some ion channels, passage through the pore is governed by a "gate," which may be opened or closed by chemical or electrical signals, temperature, or mechanical force, depending on the variety of channel. (wikidoc.org)
  • This small family of channels, normally referred to as Catsper channels, is related to the two-pore channels and distantly related to TRP channels . (wikidoc.org)
  • The architectures of the ion channel families consist of four variations built upon a common pore-forming structural theme. (aspetjournals.org)
  • The functional elements of the ion channel superfamily of proteins can be divided into three complementary aspects: ion conductance, pore gating, and regulation. (aspetjournals.org)
  • Analysis of the chick cone CNG channel gene reveals that these forms are produced by alternative splicing, which removes either one or two exons from the transcript. (jneurosci.org)
  • Gene Ontology (GO) annotations related to this gene include voltage-gated potassium channel activity and cGMP binding . (genecards.org)
  • This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. (genscript.com)
  • HCN1 includes Hyperpolarization-activated cation channels of the HCN gene family, which contribute to spontaneous rhythmic activity in both heart and brain. (thermofisher.com)
  • The HCN4 gene provides instructions for making a channel that transports positively charged atoms (ions) into heart muscle cells. (medlineplus.gov)
  • Antigen standard for potassium voltage-gated channel, shaker-related subfamily, member 10 (KCNA10) is a lysate prepared from HEK293T cells transiently transfected with a TrueORF gene-carrying pCMV plasmid and then lysed in RIPA Buffer. (creativebiomart.net)
  • We report a complete nucleotide sequence of a plasmid carrying the multi-resistance gene cfr. (jove.com)
  • For cAMP detection the recipient cells were transfected with a reporter gene, the cyclic nucleotide-modulated channel from sea urchin sperm (SpIH). (nih.gov)
  • Voltage-gated potassium (K V ) channels, first identified as the gene encoding the Shaker mutation in the fruit fly Drosophila , exemplify the second structural architecture in the ion channel superfamily. (aspetjournals.org)
  • Cyclic nucleotide-gated cation channels mediate sensory transduction in vertebrate photoreceptors and olfactory epithelium. (unthsc.edu)
  • RT "Nuclear-localized cyclic nucleotide-gated channels mediate symbiotic RT calcium oscillations. (genome.jp)
  • Cyclic nucleotide-gated (CNG) channels mediate the transduction of light signals to electrical signals in vertebrate photoreceptors. (upenn.edu)
  • This study explored the molecular identity of channels that mediate adenosine-induced Ca 2+ influx in vascular endothelial cells. (ahajournals.org)
  • Virtually nothing is known about the molecular identity of channels that mediate adenosine-induced Ca 2+ influx in endothelial cells. (ahajournals.org)
  • Our results demonstrated that CNG channels, especially CNGA2, mediate the adenosine-induced Ca 2+ influx in these cells, and that CNG channels may play an important role in endothelium-dependent vasorelaxation in response to A 2 adenosine receptor agonists. (ahajournals.org)
  • In the ADAM11 mutant, GABAergic release was not altered, but the ultrarapid electrical signal was absent, demonstrating that the dense presynaptic cluster of Kv1 ion channels at these terminals mediate electrical transmission. (jneurosci.org)
  • In mammalian axons, homomeric and heteromeric Kv1 channels of the Shaker superfamily mediate a range of fast activating, slowly inactivating (delayed rectifier) repolarizing currents. (jneurosci.org)
  • The vanilloid receptor-related TRP channels (TRPV1-6) mediate thermosensation, pain perception and epithelial Ca 2+ entry. (biologists.org)
  • Because "voltage-gated" channels underlie the nerve impulse and because "transmitter-gated" channels mediate conduction across the synapses , channels are especially prominent components of the nervous system . (wikidoc.org)
  • In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. (genecards.org)
  • The exquisite regulation of different CNG channels by divalent cations, calmodulin, phosphorylation and phospholipids allows these proteins to carry out disparate physiological functions with high precision. (els.net)
  • Ion channels are membrane proteins that allow ions to diffuse across cellular membranes in a regulated manner. (els.net)
  • Ion channels are membrane proteins that conduct ions across lipid membranes through pores in the channel proteins. (ucdavis.edu)
  • Ion channels are membrane proteins that control the flow of ions such as K + , Na + , Ca 2+ , and Cl- across the cell membrane. (utsouthwestern.edu)
  • Uptake and distribution of cationic nutrients mainly relies on membrane-localized cation transporter proteins. (pubmedcentralcanada.ca)
  • The underlying mechanisms rely primarily on elevating guanosine 3′,5′-cyclic monophosphate due to the stimulation of soluble guanylyl cyclase, inhibiting mitochondria respiration by the action on cytochrome C oxidase, and nitrosylating proteins and enzymes. (springer.com)
  • Our analysis found that several ion channels and a class of thioesterases constitute the possible cyclic nucleotide binding proteins in plants. (biomedcentral.com)
  • Type I cells express a large number of proteins (reviewed in Reference 3 ), among them T1-α ( 6 ), aquaporin 5 (AQP-5) ( 7 ), functional ion channels ( 8 ), caveolins, adenosine receptors ( 9 ), and multidrug resistance genes. (pubmedcentralcanada.ca)
  • A family of hyperpolarization-activated mammalian cation channels. (ebi.ac.uk)
  • His laboratory currently studies various ion channels, including Torpedo and mammalian CLC chloride channels, cyclic nucleotide gated channels and calcium-activated chloride channels, to name a few. (ucdavis.edu)
  • Another CLC channel studied in Dr. Chen's laboratory is called CLC-1, which is expressed abundantly in mammalian skeletal muscles. (ucdavis.edu)
  • Absolutely resistant against mammalian cyclic nucleotide-dependent phosphodiesterases, no metabolic side effects. (biolog.de)
  • Cyclic nucleotides exert their cellular functions through three major classes of cellular receptors, one of them is the cyclic nucleotide-gated (CNG) channels. (biomol.com)
  • 9-12 CNG channels are activated by cAMP and cGMP, 13 the levels of which are elevated when endothelial cells are exposed to adenosine. (ahajournals.org)
  • Increase in cAMP and cGMP concentration activates cyclic nucleotide gated channels (CNGC), which causes influx of Ca 2+ into the cytosol. (els.net)
  • Ali R, Zielinski RE and Berkowitz GA (2006) Expression of plant cyclic nucleotide‐gated cation channels in yeast. (els.net)
  • Although several ion channels have been reported to be directly modulated by calcium-calmodulin, they have not been conclusively shown to bind calmodulin, nor are the modulatory mechanisms understood. (elsevier.com)
  • Study of the olfactory cyclic nucleotide-activated cation channel, which is modulated by calcium-calmodulin, indicates that calcium-calmodulin directly binds to a specific domain on the amino terminus of the channel. (elsevier.com)
  • The chick cone CNG channel and the pineal splice form are both modulated by Ca 2+ /calmodulin (CaM). (jneurosci.org)
  • He discovered calmodulin modulation of cyclic nucleotide-gated cation channels critical in visual and olfactory sensory adaptation mechanisms. (ucdavis.edu)
  • The discovery opened the field of calmodulin modulation of ion channels. (ucdavis.edu)
  • CNG channels are also moderately sensitive to block by some other inhibitors of the L-type calcium channel (e.g., nifedipine), the local anesthetic tetracaine, and calmodulin antagonists ( Kaupp and Seifert, 2002 ). (aspetjournals.org)
  • Kurosaki, F. , Kaburaki, H. , Nishi, A. 1994 Involvement of plasma membrane-located calmodulin in the response decay of cyclic nucleotide-gated cation channel of cultured carrot cells. (wiley.com)
  • 2,3 Cyclic GMP is degraded by cGMP-hydrolyzing phosphodiesterases (PDEs). (ahajournals.org)
  • Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. (springer.com)
  • cGMP plays a role in sensory signaling and plasticity by regulating ion channels, phosphodiesterases, and kinases. (genetics.org)
  • Such a reporter can be used to illuminate how producers (guanylyl cyclases) and degraders (phosphodiesterases) of cGMP shape the landscape of this cyclic nucleotide in neurons. (genetics.org)
  • 11] "Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. (tcdb.org)
  • A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate. (inta.cl)
  • Sensory transduction in retinal photoreceptors and olfactory sensory neurons (OSNs) is mediated by ion channels that are gated open by the intracellular messengers cGMP and cAMP, respectively. (jneurosci.org)
  • Cyclic nucleotide-gated (CNG) channels are crucial for sensory transduction in rod and cone photoreceptors and olfactory sensory neurons. (rupress.org)
  • CNG channels are expressed in the cilia of olfactory neurones and in outer segments of rod and cone photoreceptor neurones, where they play key roles in sensory transduction. (aspetjournals.org)
  • Ion channel function underlies many biological processes such as the excitation of nerve and muscle cells, the secretion of hormones, and sensory transduction. (utsouthwestern.edu)
  • M. Driscoll, H.A. Thieringer, S. Sahota, and I. Mano , C. elegans Members of the DEG/EnaC Channel Superfamily: Form and Function. (elsevier.com)
  • Transient receptor potential (TRP) channels are members of the superfamily of hexahelical cation channels. (biologists.org)
  • Here we review the molecular and evolutionary relationships among the families within the voltage-gated-like (VGL 1 ) ion channel superfamily. (aspetjournals.org)
  • HCN channels exhibit weak selectivity for potassium over sodium ions. (ebi.ac.uk)
  • The HCN4 channel allows potassium and sodium ions to flow into cells of the SA node. (medlineplus.gov)
  • This nonconventional axo-axonic contact extends beyond the perisomatic chemical GABAergic synaptic boutons to the distal AIS, lacks both sodium channels and local exocytotic machinery, and yet contains a dense cluster of voltage-gated potassium channels whose functional contribution is unknown. (jneurosci.org)
  • SIGNIFICANCE STATEMENT This study identifies ADAM11 as the first essential molecule for the proper localization of potassium ion channels at presynaptic nerve terminals, where they modulate excitability and the release of neural transmitters. (jneurosci.org)
  • Jiang Y, A Lee, J Chen, M Cadene, BT Chaitand R MacKinnon (2002) Crystal structural and mechanism of a calcium-gated potassium channel . (utsouthwestern.edu)
  • Jiang Yand R MacKinnon (2000) The barium site in a potassium channel by X-ray crystallography . (utsouthwestern.edu)
  • Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, Cohen RA (1994) Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. (springer.com)
  • In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. (hindawi.com)
  • Several other families of ion channels also have this architecture, including calcium-activated potassium (K Ca ) channels, cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels, and transient receptor potential (TRP) channels ( Fig. 1 and see below). (aspetjournals.org)
  • The hyperpolarisation-activated cation current (termed I(f), I(h), or I(q)) plays a key role in the initiation and modulation of cardiac and neuronal pacemaker depolarisations. (ebi.ac.uk)
  • Cardiac HCN channels: structure, function, and modulation. (ebi.ac.uk)
  • The four members of this family, HCN1-4, show distinct biophysical properties which are most evident in the kinetics of activation and deactivation, the sensitivity towards cyclic nucleotides and the modulation by tyrosine phosphorylation. (mdpi.com)
  • Our recent work shows that CNG channels in rod outer segments are subject to modulation by changes in tyrosine phosphorylation, the final step in a biochemical cascade in which neuromodulators can alter the rod light response (Savchenko, Kraft, Molokanova, Kramer, manuscript in preparation). (rupress.org)
  • In addition to basic understanding, the significance of learning about HCN channel modulation by cAMP is that there may be therapeutic advantage of controlling heart rate via drug interaction with the cyclic nucleotide binding pocket. (ubc.ca)
  • The cytotoxic Ca 2+ response is generally more pronounced and sustained than physiological Ca 2+ signalling and can be due to excessive Ca 2+ influx by plasma membrane ion channels, or to inappropriate Ca 2+ release from intracellular stores, notably, the endoplasmic reticulum ( Orrenius et al , 2003 ). (embopress.org)
  • Binding of cGMP to a plasma membrane cation channel maintains a small calcium flux. (sciencemag.org)
  • Voltage-gated ion channels activate/inactivate depending on the voltage gradient across the plasma membrane, while ligand-gated ion channels activate/inactivate depending on binding of ligands to the channel. (wikidoc.org)
  • 1 The CNG channels are non-selective cation channels facilitating the influx of Na +and Ca 2+ ions, following activation by intracellular cyclic nucleotides. (biomol.com)
  • Therefore, GAF and CNB domains have evolved independently to bind cyclic nucleotides. (biomedcentral.com)
  • This entry represents HCN4, which belongs to the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel family. (ebi.ac.uk)
  • Netter MF, Zuzarte M, Schlichthörl G, Klöcker N, Decher N. The HCN4 channel mutation D553N associated with bradycardia has a C-linker mediated gating defect. (medlineplus.gov)
  • HCN1 is the fastest activating channel with an activation constant τ in the range of 30-300 ms, whereas HCN4 represents the most slowly activating isoform with τ between 300 ms and several s. (mdpi.com)
  • HCN4 channels are the predominant HCN isoform in the sinoatrial node and contribute to pacemaker current that controls rhythmic activity in the heart and brain. (creativebiomart.net)
  • CNG channels expression was also found in the hippocampus, cortex, Purkinje cells and other neural derived tissues. (biomol.com)
  • Moosmang S, Stieber J, Zong X, Biel M, Hofmann F, Ludwig A. Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues. (ebi.ac.uk)
  • 4] "Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells. (tcdb.org)
  • H. O'Brodovich, B. Rafii, A.K. Tanswell, and O. Pitkänen , Induction of Epithelial Sodium Channel Expression and Sodium Transport in Distal Lung Epithelia by Oxygen. (elsevier.com)
  • In addition, the expression profile of the channels is markedly different and characteristic for each isoform. (mdpi.com)
  • Previous reports showed that expression of HCN channels on the cell surface is uneven in some neurons. (hindawi.com)
  • Expression and kinetics of HCN channels are affected by unusual neuronal activity like epilepsy and environmental stimuli. (hindawi.com)
  • Cyclic nucleotides are small ligands used to control the gating of CNG channels. (els.net)
  • Photoreceptor channels strongly discriminate between cGMP and cAMP, whereas the olfactory channel is almost equally sensitive to both ligands. (aspetjournals.org)
  • Ligand-gated channels are diverse with respect to ligands that cause them to open. (utsouthwestern.edu)
  • The common location of the ligand-binding domain in nearly all cases implies a general mechanism by which different ligands open cation channels. (utsouthwestern.edu)
  • Molecular characterization of the cyclic nucleotide-gated. (ubc.ca)
  • In spite of these comprehensive investigations the molecular structure of I h -channels was completely unknown until recently. (tum.de)
  • One standard approach in Dr. Chen's lab is to mutate the structure of the channel, often according to disease mutation, and then study the mutational consequence in the channel to understand the molecular pathophysiology of the channelopathy. (ucdavis.edu)
  • Two molecular mechanisms are crucial for the proper physiological function of retinal CNG channels. (upenn.edu)
  • This paper provides a molecular framework for the discussion of cyclic nucleotide function in plants, and resolves a longstanding debate about the presence of a cyclic nucleotide dependent kinase in plants. (biomedcentral.com)
  • For voltage-dependent gating, inward movement of S4 segment in response to hyperpolarization is reported [ 7 - 9 ], but molecular aspects of channel opening are still unknown. (hindawi.com)
  • Residues spacefilled in red represent residues in the selectivity filter accessible to cysteine modification in closed CNG channels. (els.net)
  • or = Cx40), suggesting that these channels have distinctly different selectivity for negatively charged larger solutes involved in metabolic/biochemical coupling. (nih.gov)
  • Cx26 ≥ Cx40, suggesting that these channels have distinct selectivity for larger solutes. (nih.gov)
  • CNG channels are ion channels regulated by the direct binding of cyclic nucleotides. (els.net)
  • The direct binding of cyclic AMP upon adrenaline release also enhances channel opening, leading to an increased frequency of action potential. (ubc.ca)
  • The influx of Ca2+ through these channels during the odorant response may rise to a sufficiently high concentration at the intracellular membrane surface to contribute to the desensitization of the odorant-induced response. (rupress.org)
  • Researchers speculate that the defective channels allow a huge influx of cations into cones, which ultimately causes these cells to self-destruct (undergo apoptosis). (medlineplus.gov)
  • Methods and Results- Adenosine-induced Ca 2+ influx was markedly reduced by L- cis -diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated (CNG) channels, in H5V endothelial cells and primary cultured bovine aortic endothelial cells (BAECs). (ahajournals.org)
  • A CNGA2-specific siRNA markedly decreased the Ca 2+ influx and the cation current in H5V cells. (ahajournals.org)
  • Conclusion- CNGA2 channels play a key role in adenosine-induced endothelial Ca 2+ influx and vasorelaxation. (ahajournals.org)
  • 13 In the present study, we tested the hypothesis that CNG channels are involved in adenosine-induced Ca 2+ influx in vascular endothelial cells. (ahajournals.org)
  • Calcium signals are generated through the coordinated action of calcium influx channels and calcium efflux transporters. (els.net)
  • Plants possess Ca 2+ ‐permeable influx channels (blue rectangles), as well as vacuolar Ca 2+ /H + exchangers (green cylinder) and Ca 2+ pumps (red ovals) for extruding Ca 2+ . (els.net)
  • The whole-cell inward currents in A549 cells that are stimulated by 8-Br-cGMP, are inhibited by 1-cis-diltiazem with an IC 50 of 87 μM, by 2'4'-dichlorobenzamil with an IC 50 of 38 μM and by amiloride with an IC 50 of 32 μM suggesting that these airway cells contain cyclic nucleotide-gated cation channels. (elsevier.com)
  • Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP 2 , and TRIP8b. (hindawi.com)
  • The voltage-dependent opening of the HCN channels is directly regulated by the binding of cAMP. (ebi.ac.uk)
  • Binding of cAMP to the CNBD speeds up channel opening and shifts the voltage-dependence of activation to more positive voltages [ PMID: 18953682 ]. (ebi.ac.uk)
  • We present the biophysical investigation of the mechanism underlying voltage sensitivity of ion channel block. (upenn.edu)
  • However, these mutant channels can open in response to voltage at positive potentials only when bound by cGMP. (upenn.edu)
  • This mutation-caused voltage gating reflects the inherent voltage gating capabilities of the wild-type channel, which must be suppressed to avoid their closure in a physiological setting. (upenn.edu)
  • It blocks CNG channels in a voltage-dependent manner at micromolar concentration ( Haynes, 1992 ). (aspetjournals.org)
  • Bruggemann, A. , Pardo, L.A. , Stuhmer, W. , Pongs, O. 1993 Ether-a-go-go encodes a voltage-gated channel permeable to K + and Ca 2+ and modulated by cAMP. (wiley.com)
  • Hoshi, T. 1995 Regulation of voltage dependence of the KAT1 channel by intracellular factors. (wiley.com)
  • VVCC, vacuolar voltage‐gated Ca 2+ channel. (els.net)
  • There are two general gating mechanisms of cation channels: ligand gating and voltage gating. (utsouthwestern.edu)
  • In voltage gating, changes in the membrane voltage open and close the channel. (utsouthwestern.edu)
  • Jiang Y, A Lee, J Chen, V Ruta, M Cadene, BT Chaitand R MacKinnon (2003) X-ray structure of a voltage-dependent K+ channel . (utsouthwestern.edu)
  • Jiang Y, V Ruta, J Chen, A Leeand R MacKinnon (2003) The principle of gating charge movement in a voltage-dependent K+ channel . (utsouthwestern.edu)
  • Ruta V, Y Jiang, A Lee, J Chenand R MacKinnon (2003) Functional analysis of an archaebacterial voltage-dependent K+ channel . (utsouthwestern.edu)
  • Owing to cyclic nucleotide responsiveness, the current-voltage relationship and kinetics of I f change with autonomic tone, such that diastolic depolarization occurs more rapidly with increasing sympathetic tone and more slowly with enhanced vagal tone. (onlinejacc.org)
  • The general structure of HCN channels resembles that of the voltage-gated K + channels. (hindawi.com)
  • Cyclic-AMP-(cAMP-) binding site locates near the C terminus, and cAMP affects the voltage dependence of activation in some HCN channel isoforms [ 10 ]. (hindawi.com)
  • voltage-gated channels open and close in response to membrane potential . (wikidoc.org)
  • Voltage-gated calcium (Ca V ) channels have a similar structure ( Fig. 1 ). (aspetjournals.org)
  • To regulate intracellular cation homeostasis, plants have evolved several distinct classes of transporters to facilitate the movement of monovalent and divalent cations across cellular membranes. (biomedcentral.com)
  • CNG channels pass monovalent cations, such as Na + and K + , but do not discriminate between them. (aspetjournals.org)
  • All three homotypic channels are poorly selective toward monovalent cations as illustrated by the Na+/K+ conductance ratios. (nih.gov)
  • We also discuss in detail the different aspects of HCN channel physiology in the heart and nervous system. (nih.gov)
  • Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3. (uniprot.org)
  • The d - cis -enantiomer of diltiazem that is used therapeutically as a blocker of the L-type calcium channel is much less effective than the l - cis -enantiomer in blocking CNG channels. (aspetjournals.org)
  • Cellular calcium uptake is a controlled physiological process mediated by multiple ion channels. (embopress.org)
  • The mainstays of therapy include negative chronotropic agents such as beta-blockers and calcium channel blockers, often ineffectual at doses high enough to cause intolerable side effects. (onlinejacc.org)
  • Light promotes the degradation of cGMP, allowing these cyclic nucleotide-gated channels to close, resulting in hyperpolarization and a fall in intracellular calcium concentration. (sciencemag.org)
  • Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. (embl.de)
  • Cyclic nucleotide-gated channels of rat olfactory receptor cells: divalent cations control the sensitivity to cAMP. (rupress.org)
  • Not surprisingly, the four HCN isoforms vary in several biophysical properties including the time course of activation and deactivation and the sensitivity towards cAMP (cyclic adenosine monophosphate). (mdpi.com)
  • In addition to preventing PTK-catalyzed changes in cGMP sensitivity when ATP is present, genistein also inhibits channel gating in the absence of ATP. (rupress.org)
  • CNG channels reveal a higher sensitivity for cGMP than for cAMP. (aspetjournals.org)
  • The analysis of the contribution of cytosolic N- and C-termini as well as of the transmembrane domains suggests a complex mechanism of channel assembly. (biologists.org)
  • The cyclic nucleotide-gated ion channels (CNGCs) maintain cation homeostasis essential for a wide range of physiological processes in plant cells. (biomedcentral.com)
  • The involvement of cyclic nucleotide gated ion channels (CNGCs) in the signal transduction of animal light and odorant perception is well documented. (pubmedcentralcanada.ca)
  • CNG ion channels are essential in visual and olfactory signal transduction. (biomol.com)
  • Cyclic nucleotide-gated (CNG) channels play central roles in visual and olfactory signal transduction. (jneurosci.org)
  • This binding reduces the effective affinity of the channel for cyclic nucleotides, apparently by acting on channel gating, which is tightly coupled to ligand binding. (elsevier.com)
  • Ligand-binding domain subregions contributing to bimodal agonism in cyclic nucleotide-gated channels. (nih.gov)
  • Cyclic nucleotide-gated (CNG) channels bind cGMP or cAMP in a cytoplasmic ligand-binding domain (BD), and this binding typically increases channel open probability (P(o)) without inducing desensitization. (nih.gov)
  • The extent of ligand discrimination varies significantly between the individual CNG channel types. (aspetjournals.org)
  • In ligand-gated channels, a small molecule such as a neurotransmitter or second messenger binds to the channel and causes it to open. (utsouthwestern.edu)
  • The type of domain varies, depending on whether the channel is gated by cyclic nucleotides, by Ca 2+ , or by a different ligand. (utsouthwestern.edu)
  • BK channels) contain a conserved, C-terminal ligand-binding domain that we call the RCK domain, for regulation of K + conductance. (utsouthwestern.edu)
  • The research in my lab is to understand the mechanisms of ligand-dependent gating in K + channels opened by RCK domains. (utsouthwestern.edu)
  • The results also indicate that divalent cation effects on cyclic nucleotide-gated channels may depend on the sequence of pre-exposure to other divalent cations. (rupress.org)
  • In some cases, fewer of the altered channels reach the cell membrane, where they are needed to transport ions. (medlineplus.gov)
  • In other cases, the channel is in the right place but has an abnormal structure that changes how ions flow through it. (medlineplus.gov)
  • Permeation describes the ability of ion channels to selectively determine which ions can move through them. (els.net)
  • Gating is the process by which ion channels open and close to control the flow of ions. (els.net)
  • For example, how do ion channels open and close their pores, and how do ion channels select particular ions to pass through their open pores? (ucdavis.edu)
  • Ion channels regulate the flow of ions across the membrane in all cells. (wikidoc.org)
  • In addition, ion channels figure in a wide variety of biological processes that involve rapid changes in cells, such as cardiac , skeletal , and smooth muscle contraction , epithelial transport of nutrients and ions, T-cell activation and pancreatic beta-cell insulin release. (wikidoc.org)
  • Ion channels may be classified by the nature of their gating, the species of ions passing through those gates, and the number of gates (pores). (wikidoc.org)
  • In vertebrates, the HCN channel family comprises four members (HCN1-4) [ PMID: 12161074 ]. (ebi.ac.uk)
  • Whereas HCN3 seems to be specifically expressed in neurons, the other three channels (HCN1, 2, and 4) have been detected in both heart and brain [ PMID: 9634236 , PMID: 11248683 ]. (ebi.ac.uk)
  • HCN1 is a member of a family of pacemaker channels activated by hyperpolarization and regulated by cyclic nucleotides. (thermofisher.com)
  • In mammals, the HCN channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. (nih.gov)
  • The cyclic adenosine monophosphate (cAMP) signaling pathway is involved in numerous processes and is widely regarded as the "classical" second messenger signaling pathway. (sciencemag.org)
  • HCN pacemaker channels generate the "funny" current that is responsible for initiation and regulation of electrical activity in the heart and the nervous system. (ubc.ca)
  • Cyclic Nucleotide-Gated Cation Channels" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)

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