Ion Channels
Cations
TRPM Cation Channels
Cyclic Nucleotide Phosphodiesterases, Type 1
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.
Calcium Channels
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.
Cyclic GMP
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)
TRPC Cation Channels
Cyclic Nucleotide-Gated Cation Channels
3',5'-Cyclic-AMP Phosphodiesterases
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.
Nucleotides
Ion Channel Gating
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.
2',3'-Cyclic-Nucleotide Phosphodiesterases
Cyclic AMP
TRPV Cation Channels
Cations, Divalent
Cyclic Nucleotide Phosphodiesterases, Type 3
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.
Molecular Sequence Data
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.
Calcium
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.
Phosphoric Diester Hydrolases
Potassium Channels, Inwardly Rectifying
Phosphodiesterase Inhibitors
Calcium Channel Blockers
Cyclic Nucleotide Phosphodiesterases, Type 2
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.
Cations, Monovalent
Chloride Channels
Amino Acid Sequence
Potassium Channel Blockers
Dibutyryl Cyclic GMP
Membrane Potentials
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).
Patch-Clamp Techniques
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.
Cyclic Nucleotide Phosphodiesterases, Type 4
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.
Transient Receptor Potential Channels
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.
Electrophysiology
Potassium Channels, Voltage-Gated
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Calcium Channels, L-Type
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.
Flufenamic Acid
Adenosine Triphosphate
TRPP Cation Channels
Acid Sensing Ion Channels
Potassium
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.
1-Methyl-3-isobutylxanthine
KATP Channels
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.
3',5'-Cyclic-GMP Phosphodiesterases
Potassium Channels, Calcium-Activated
Cyclic Nucleotide Phosphodiesterases, Type 7
Sodium
Cells, Cultured
Oocytes
Sodium Channel Blockers
Cell Membrane
Mutation
Magnesium
Cyclic Nucleotide Phosphodiesterases, Type 5
Cloning, Molecular
Bucladesine
Calmodulin
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.
Base Sequence
Cyclic IMP
Binding Sites
Ion Transport
Epithelial Sodium Channels
Shaker Superfamily of Potassium Channels
Theophylline
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.
Xenopus laevis
Dose-Response Relationship, Drug
Polymorphism, Single Nucleotide
Calcium Channels, N-Type
Large-Conductance Calcium-Activated Potassium Channels
Protein Structure, Tertiary
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.
Calcium Channels, T-Type
Xenopus
Ether-A-Go-Go Potassium Channels
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.
Barium
Models, Molecular
Cattle
Gadolinium
Protein Binding
8-Bromo Cyclic Adenosine Monophosphate
RNA, Messenger
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.
Calcium Channel Agonists
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.
Hydrogen-Ion Concentration
Sequence Homology, Amino Acid
Neurons
Cell Membrane Permeability
Rabbits
Rats, Sprague-Dawley
Kv1.2 Potassium Channel
Kv1.3 Potassium Channel
Kv1.1 Potassium Channel
Kv1.5 Potassium Channel
Degenerin Sodium Channels
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.
Guinea Pigs
Protein Conformation
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).
Transfection
Cation Transport Proteins
Signal Transduction
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.
Manganese
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)
Models, Biological
Purine Nucleotides
Cyclic AMP-Dependent Protein Kinases
Second Messenger Systems
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.
Amiloride
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)
Colforsin
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.
Membrane Proteins
Adenylate Cyclase
Mutagenesis, Site-Directed
Structure-Activity Relationship
Escherichia coli
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.
Cyclic GMP-Dependent Protein Kinases
Carbachol
KCNQ Potassium Channels
Cesium
Sequence Alignment
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.
Action Potentials
Shab Potassium Channels
Organic Cation Transport Proteins
Myocardium
DNA
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).
Receptors, Purinergic P2
Receptors, Purinergic P2X
Ions
Enzyme Activation
Guanylate Cyclase
Small-Conductance Calcium-Activated Potassium Channels
Pyrrolidinones
Organic Cation Transporter 1
Kv1.4 Potassium Channel
Potassium Channels
Isoenzymes
Enzyme Inhibitors
Adenosine Diphosphate
Calcium Signaling
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.
Receptors, Purinergic P2X4
Guanine Nucleotide Exchange Factors
Oxocins
Muscle, Smooth
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)
Cricetinae
Shaw Potassium Channels
Ryanodine Receptor Calcium Release Channel
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.
Lanthanum
Protein Kinases
DNA, Complementary
Rats, Wistar
Protein Subunits
Brain
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.
Isoproterenol
Lipid Bilayers
Kidney
Cyclic CMP
HEK293 Cells
Receptors, Purinergic P2X7
Permeability
Shal Potassium Channels
Receptors, Drug
Papaverine
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.
Tetrodotoxin
Phosphorylation
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Cytosol
Photoreceptor Cells
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.
Substrate Specificity
KCNQ2 Potassium Channel
Guanosine Triphosphate
DNA Primers
Nifedipine
Strontium
Sequence Homology, Nucleic Acid
Nucleic Acid Conformation
Sequence Analysis, DNA
Ruthenium Red
Calcium Channels, P-Type
Gene Expression
NAV1.5 Voltage-Gated Sodium Channel
Nitroprusside
Boron Compounds
Thapsigargin
Adenosine Monophosphate
Intermediate-Conductance Calcium-Activated Potassium Channels
Protein Structure, Secondary
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)
Cyclic nucleotide-gated cation channel expression in embryonic chick brain<...
CNGA4 - Cyclic nucleotide-gated cation channel alpha-4 - Homo sapiens (Human) - CNGA4 gene & protein
HCN4 - Wikipedia
Channelpedia
Molecular Mechanisms of a Retinal Cyclic Nucleotide-Gated Channel by Juan R. Martinez-Francois
Tetracaine Reports a Conformational Change in the Pore of Cyclic Nucleotide-gated Channels | JGP
Cyclic Nucleotide-Gated Channels in Plants - Insights from Suppressor Screens of Two Lesion Mimic Mutants, cpr22 and dnd1;...
UC Davis Department of Neurology - Neuroscience Researchers - Chen
Additional file 5: of A comparison of heat-stress transcriptome changes between wild-type Arabidopsis pollen and a heat...
Seminar: cGMP/PKG signaling regulation of endoplasmic reticulum homeostasis in CNG channel deficiency - Webvision
The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry
Turkish Neurosurgery
Activity-Dependent Regulation of the Proapoptotic BH3-Only Gene egl-1 in a Living Neuron Pair in Caenorhabditis elegans | G3:...
Mechanism of Cone Degeneration Resulting from CNG Channel Deficiency - Xi-Qin Ding
Publications by: J.B. Furness Also publishes as (John Furness) - [email protected]
Disease Lesion Mimic Mutants of Maize
anti-HCN3 antibody [S141-28] | GeneTex
Mutagenetix > Incidental...
CNGA1 Gene - GeneCards | CNGA1 Protein | CNGA1 Antibody
CNGB3 Gene - GeneCards | CNGB3 Protein | CNGB3 Antibody
Hyperpolarization-activated cyclic nucleotide-gated channel mRNA and protein expression in large versus small diameter dorsal...
Decreased hyperpolarization-activated cyclic nucleotide-gated channels are involved in bladder dysfunction associated with...
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Regularizing firing patterns of rat subthalamic neurons ameliorates parkinsonian motor deficits
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Regularizing firing patterns of rat subthalamic neurons ameliorates parkinsonian motor deficits
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Gating mechanisms in hyperpolarization-activated cyclic nucleotide-gat by Sriharsha Vemana
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Two Alternatively Spliced Forms of the cGMP-Gated Channel α-Subunit from Cone Photoreceptor Are Expressed in the Chick Pineal...
Properties of Hyperpolarization-Activated Pacemaker Current Defined by Coassembly of Hcn1 and Hcn2 Subunits and Basal...
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Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach
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Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach
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Patients and animal models of CNGβ1-deficient retinitis pigmentosa support gene augmentation approach
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Volume 128, Issue 1
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CNGA3 HUMAN
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). ...
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Ion - Wikipedia, le encyclopedia libere
... 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[*], ...
TRPM
... 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 channel • Cyclic 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, ...
CRP and RPL13A Interaction - Wiki-Pi
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 ...
HMG20A and PTH2R Interaction - Wiki-Pi
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 ...
RPS8 and CALM1 Interaction - Wiki-Pi
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 ...
SNTA1 and CALM1 Interaction - Wiki-Pi
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 ...
CALM3 and IQCE Interaction - Wiki-Pi
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 ...
tag :: dependent | BibSonomy
CSPN)(FPGA)(SDDO)BlockControlledDataDependentFieldHybridOperationSwitchablearrayciphergatemodelnetworkspermutationprogrammable ... antigenicbinding,cchemistry,corecrystal-structure,dependentderivatives,discovery,dqcauchilehcvhepatitisns5bnucleosidenucleotide ... 1Cation-Dependent Light-Induced Halide Demixing in Hybrid Organic-Inorganic Perovskites. ...
SubunitProteinNonselective cation channelsArabidopsisHyperpolarization activated cyclic nucleotide gatedCnga3SubunitsHcn2PoreGeneMediatePhotoreceptor cGMP-gated cProteinsMammalianReceptorsCAMP and cGMPPlant cyclic nucleotideCalmodulinPhosphodiesterasesAchromatopsiaSensory transductionSuperfamilyPotassiumModulationPlasma membraneIntracellular cyclic nucleotidesBind cyclic nucleotidesHCN4ExpressionLigandsMolecularSelectivityDirect binding oInfluxContain cyclicVoltageMonovalentPhysiologyCalciumVertebrateSensitivityTransmembraneCNGCsVisual and olfactory signal transductionLigandDivalent cationIonsHCN1Adenosine monophosphatePacemaker channelsMeSH
Subunit40
- 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)
Protein35
- 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)
Nonselective cation channels1
- CNGCs, nonselective cation channels that open upon cyclic nucleotide binding, are particularly important in the olfactory and visual systems ( 3 ). (sciencemag.org)
Arabidopsis6
- 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 gated12
- 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)
Cnga32
- 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)
Subunits26
- 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)
Hcn23
- 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)
Pore15
- 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)
Gene9
- 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)
Mediate10
- 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)
Photoreceptor cGMP-gated c1
- 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)
Proteins8
- 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)
Mammalian4
- 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)
Receptors1
- 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)
CAMP and cGMP2
- 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)
Plant cyclic nucleotide1
- Ali R, Zielinski RE and Berkowitz GA (2006) Expression of plant cyclic nucleotide‐gated cation channels in yeast. (els.net)
Calmodulin7
- 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)
Phosphodiesterases4
- 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)
Achromatopsia2
- 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 transduction4
- 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)
Superfamily3
- 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)
Potassium9
- 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)
Modulation5
- 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)
Plasma membrane3
- 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)
Intracellular cyclic nucleotides1
- 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)
Bind cyclic nucleotides1
- Therefore, GAF and CNB domains have evolved independently to bind cyclic nucleotides. (biomedcentral.com)
HCN44
- 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)
Expression7
- 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)
Ligands4
- 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)
Molecular6
- 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)
Selectivity3
- 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)
Direct binding o2
Influx8
- 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)
Contain cyclic2
- 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)
Voltage19
- 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)
Monovalent3
- 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)
Physiology1
- We also discuss in detail the different aspects of HCN channel physiology in the heart and nervous system. (nih.gov)
Calcium5
- 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)
Vertebrate1
- Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. (embl.de)
Sensitivity4
- 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)
Transmembrane1
- 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)
CNGCs2
- 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)
Visual and olfactory signal transduction2
- 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)
Ligand8
- 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)
Divalent cation1
- 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)
Ions8
- 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)
HCN14
- 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)
Adenosine monophosphate1
- 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)
Pacemaker channels1
- 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)
MeSH1
- Cyclic Nucleotide-Gated Cation Channels" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)