Neurons in the OLFACTORY EPITHELIUM with proteins (RECEPTORS, ODORANT) that bind, and thus detect, odorants. These neurons send their DENDRITES to the surface of the epithelium with the odorant receptors residing in the apical non-motile cilia. Their unmyelinated AXONS synapse in the OLFACTORY BULB of the BRAIN.
A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.
The volatile portions of substances perceptible by the sense of smell. (Grant & Hackh's Chemical Dictionary, 5th ed)
Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.
That portion of the nasal mucosa containing the sensory nerve endings for SMELL, located at the dome of each NASAL CAVITY. The yellow-brownish olfactory epithelium consists of OLFACTORY RECEPTOR NEURONS; brush cells; STEM CELLS; and the associated olfactory glands.
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
Proteins, usually projecting from the cilia of olfactory receptor neurons, that specifically bind odorant molecules and trigger responses in the neurons. The large number of different odorant receptors appears to arise from several gene families or subfamilies rather than from DNA rearrangement.
Fields of science encompassing studies and research from the disciplines of PHYSICS; CHEMISTRY; BIOLOGICAL SCIENCES; and MATHEMATICS; that are related to the planet EARTH. Subfields include atmospheric chemistry; CLIMATOLOGY; ENVIRONMENTAL SCIENCES; GEOGRAPHY; GEOLOGY; geophysics; METEOROLOGY; OCEANOGRAPHY; PALEONTOLOGY; mineralogy; and seismology.
A genus in the family Blattidae containing several species, the most common being P. americana, the American cockroach.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
Created 7 April 1992 as a result of the division of Yugoslavia.
A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.
Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.
The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
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.
A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis (ENTEROCOLITIS, PSEUDOMEMBRANOUS) in patients receiving antibiotic therapy.
Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases.
An acute inflammation of the INTESTINAL MUCOSA that is characterized by the presence of pseudomembranes or plaques in the SMALL INTESTINE (pseudomembranous enteritis) and the LARGE INTESTINE (pseudomembranous colitis). It is commonly associated with antibiotic therapy and CLOSTRIDIUM DIFFICILE colonization.
Infections with bacteria of the genus CLOSTRIDIUM.
Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.
Proteins found in any species of bacterium.
A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.
Substances causing insects to turn away from them or reject them as food.
A compound used as a topical insect repellent that may cause irritation to eyes and mucous membranes, but not to the skin.
A species of mosquito in the genus Anopheles and the principle vector of MALARIA in Africa.
Organic esters of thioglycolic acid (HS-CH2COOH).
Photosensitive afferent neurons located primarily within the FOVEA CENTRALIS of the MACULA LUTEA. There are three major types of cone cells (red, blue, and green) whose photopigments have different spectral sensitivity curves. Retinal cone cells operate in daylight vision (at photopic intensities) providing color recognition and central visual acuity.
Electrophoresis in which agar or agarose gel is used as the diffusion medium.
A light-sensitive neuroendocrine organ attached to the roof of the THIRD VENTRICLE of the brain. The pineal gland secretes MELATONIN, other BIOGENIC AMINES and NEUROPEPTIDES.
Photosensitive afferent neurons located in the peripheral retina, with their density increases radially away from the FOVEA CENTRALIS. Being much more sensitive to light than the RETINAL CONE CELLS, the rod cells are responsible for twilight vision (at scotopic intensities) as well as peripheral vision, but provide no color discrimination.
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.
Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.
Databases devoted to knowledge about specific genes and gene products.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.

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)

Second messenger, cAMP, causes the opening of cation-selective cyclic nucleotide-gated (CNG) channels and depolarization of the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory subunit of this channel which is known to play a central role in the transduction of odorant signals and subsequent adaptation. By accelerating the calcium-mediated negative feedback in olfactory signaling it allows rapid adaptation to odor stimulation and extends its range of odor detection (By similarity).
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene. There are four HCN channels. HCN4 is prominently expressed in the pace maker region of the mammalian heart. Some humans with bradycardia and Sick sinus syndrome have been shown to have mutations in their HCN4 gene. The role of HCN channels in autonomic control of heart rate is currently a matter of ongoing investigation. HCN4 has been shown to interact with HCN2. Cyclic nucleotide-gated ion channel Funny current GRCh38: Ensembl release 89: ENSG00000138622 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000032338 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M (May 1999). Two pacemaker channels from human heart with profoundly different activation kinetics. The EMBO Journal. 18 (9): 2323-9. doi:10.1093/emboj/18.9.2323. PMC 1171315 . PMID 10228147. Seifert R, Scholten A, ...
The HCN channels form the subgroup of cyclic nucleotide-gated cation channel within the large superfamily of the pore loop cation channels. Like other pore loop channels, HCN channels are complexes consisting of 4 subunits that are arranged around the ventral pore. Each HCN channe subunit consists of 3 principal structural ovules: the transmembrane core and the cystosolic amino (N) terminal and carboxyl © terminal domains. The transmembrane core is comosed of 6 transmembrane segments (S1-S6) including a positively charged voltage sensor (S4) and the ion conducting pore region between (S5 and S6. The proximal portion of the systolic C-terminal domain contains the cyclic nucleotide binding domain (CNBD), which mediates modulation by cyclic nucleotides. A highly conserved asparagine residue in the extracellular loop between S5 and the pore loop is glycosylated; this posttranstional channel modification is crucial for normal cell surface expression [1690]. ...
Cyclic nucleotide-gated (CNG) channels mediate the transduction of light signals to electrical signals in vertebrate photoreceptors. These channels are non-selective for cations and open upon cGMP binding. The intracellular cGMP concentration is elevated in darkness, and the current through CNG channels maintains the membrane of the rod photoreceptor at around -40 mV. When light enters the retina, it triggers a signal transduction cascade that decreases intracellular cGMP, and therefore CNG channels close. A reduction in CNG current hyperpolarizes the rod. Two molecular mechanisms are crucial for the proper physiological function of retinal CNG channels. First, block of these channels by physiological agents reduces membrane noise in rods. This feature enables rods to detect photons with high sensitivity. Second, CNG channels must be able to conduct current in response to the light-triggered changes in intracellular cGMP. In other words, they should open and close gradually in response to cGMP
Cyclic nucleotide-gated (CNG)1 ion channels are key players in visual and olfactory signal transduction pathways (reviewed in Lancet, 1986; Yau and Baylor, 1989; Zufall et al., 1994). Although they are only weakly voltage dependent, CNG channels have regions of sequence similarity with voltage-gated channels (Jan and Jan, 1990). One region of high conservation between CNG channels and voltage-gated channels is the P region, thought to line a portion of the ion-conducting pore. Shaker K+ channels that have had portions of their P region replaced with the corresponding region from CNG channels take on many of the permeation properties of CNG channels (Heginbotham et al., 1992). These chimeric channels become permeable to Na+ as well as to K+ and become blocked by the divalent cations Mg2+ and Ca2+. Like voltage-gated channels, CNG channels are thought to possess multi-ion pores (Furman and Tanaka, 1990; Sesti et al., 1995). The external divalent cation binding site is thought to involve the E363 ...
Ca2+ signaling is central to many aspects of plant physiology; however, the channels involved in mediating Ca2+ fluxes in plants remain largely elusive. This is at least partially due to the absence of plant homologs to many of the well-characterized Ca2+ channels present in animals. Instead, plants have expanded families of ligand-gated, non-specific cation channels such as the cyclic nucleotide-gated channels (CNGCs) and glutamate receptor-like channels (GLRs), which are hypothesized to provide Ca2+ channel function in plants. The 20 member CNGC family represents one of two large families of putative Ca2+ channels in Arabidopsis, and various isoforms have been implicated in plant development and stress-response signaling, including immunity. Among Arabidopsis CNGC mutants, cpr22 and dnd1 are the best characterized mutants that show similar autoimmunity phenotypes such as constitutive expression of PR genes and heightened accumulation of salicylic acid. To understand the regulation of plant ...
Dr. Chen earned his medical degree at National Yang-Ming University in 1986 in Taiwan and his Ph.D. at Johns Hopkins University Medical School in 1994. He then received postdoctoral training at Brandeis University (1994-1996) and spent 4 years (1996-2000) as teaching faculty at National Yang-Ming University before joining UC Davis in 2001.. During his graduate studies at Hopkins, Dr. Chen worked under Professor King-Wai Yau in the Department of Neuroscience. He discovered calmodulin modulation of cyclic nucleotide-gated cation channels critical in visual and olfactory sensory adaptation mechanisms. The discovery opened the field of calmodulin modulation of ion channels.. During his postdoctoral training at Brandeis, Dr. Chen examined the biophysical mechanism of CLC chloride channels. Since then, Dr. Chen has been well known in the field of chloride channels. He received Paul Cranefield award from Society for General Physiologists in 2004. His laboratory currently studies various ion channels, ...
Additional file 5: of A comparison of heat-stress transcriptome changes between wild-type Arabidopsis pollen and a heat-sensitive mutant harboring a knockout of cyclic nucleotide-gated cation channel 16 (cngc16)
Xi-Qin Deng, Associate Professor of Cell Biology, and the Joanne I Moore Professor of Pharmacology at University of Oklahoma Health Sciences Center will be delivering a seminar on cGMP/PKG signaling regulation of endoplasmic reticulum homeostasis in CNG channel deficiency on Wednesday, January 24th at 12:00 Noon in the Moran Eye Center auditorium.. Abstract: Mutations in the CNGA3 and CNGB3 genes that encode the cone cyclic nucleotide-gated (CNG) channel subunits account for about 80% of all cases of achromatopsia and are associated with progressive cone dystrophies. Cone photoreceptors degenerate over time in patients and in mouse models of CNG channel deficiency. Over the last several years, my laboratory has been investigating the cellular mechanisms of cone degeneration using mouse models with CNG channel deficiency. Upon binding of cyclic guanosine monophosphate (cGMP) under dark conditions, CNG channels open and permit the influx of the calcium and sodium ions necessary to maintain the ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Prenatal Expressions of Hyperpolarization-activated Cyclic-Nucleotide-Gated Channel (HCN) Genes in Dysplastic Hippocampi in Rats Cihan İŞLER, Taner TANRIVERDİ, Ersen KAVAK, Galip Zihni SANUS, Mustafa Onur ULU, Gözde ERKANLI, Ahmet KOMAN, Necla Birgül İYİSON, Mustafa UZAN Abstract ...
CNG-1 is a cyclic nucleotide-gated ion channel that is an essential component of the oxygen sensation pathway in URX (Busch et al. 2012; Couto et al. 2013). Thus, we hypothesized that perhaps egl-1 expression was driven by oxygen sensation and neuronal activity. We tested this hypothesis by quantifying reporter expression in other mutants defective in oxygen sensation, as well as in wild-type worms maintained in varying levels of environmental oxygen.. First, we quantified egl-1 reporter expression in mutants lacking gcy-35 or gcy-36. These genes encode soluble guanylyl-cyclases that heterodimerize and produce cGMP in response to binding molecular oxygen (Cheung et al. 2004). Both gcy-35 and gcy-36 are necessary for URX to respond to changes in environmental oxygen. We found that both gcy-35(ok769) and gcy-36(db42) loss-of-function mutants had a near complete lack of egl-1 reporter expression in URX (Figure 3B).. Prolonged calcium entry into URX through CNG-1 in response to long-term oxygen ...
The cone cyclic nucleotide-gated (CNG) channel is essential for central and color vision and for visual acuity. Mutations in the two channel subunits, CNGA3 and...
Cho, H-J., Staikopoulos, V., Furness, J.B., and Jennings, E.A. (2009) Inflammation-induced increase in hyperpolarization-activated, cyclic nucleotide-gated channel protein in trigeminal ganglion neurons and the effect of buprenorphine. Neuroscience, ...
1. Balague, C., Lin, B., Alcon, C., Flottes, G., and Malmstrom, S., et al. 2003. HLM1, an essential signaling component in the hypersensitive response, is a member of the cyclic nucleotide-gated channel ion channel family. Plant Cell 15:365-379.. 2. Barisic, K., Petrik, J., and Rumora, L. 2003. Biochemistry of apoptotic cell death. Acta Pharm. 53:151-164.. 3. Brodersen, P., Petersen, M., Pike, H. M., Olszak, B., and Skov, S., et al. 2002. Knockout of Arabidopsis accelerated-cell-death11 encoding a sphingosine transfer protein causes activation of programmed cell death and defense. Genes Dev. 16:490-502.. 4. Buckner, B., Johal, G. S., and Janick-Buckner, D. 2000. Cell death in maize. Physiol. Plant. 108:231-239.. 5. Buschges, R., Hollricher, K., Panstruga, R., Simons, G., and Wolter, M., et al. 1997. The barley Mlo gene: a novel control element of plant pathogen resistance. Cell 88:695-705.. 6. Cory, S., and Adams, J. M. 2002. The Bcl2 family: Regulators of the cellular life-or-death switch. Nat. ...
HCN3 antibody [S141-28] (hyperpolarization-activated, cyclic nucleotide-gated K+ 3) for ICC/IF, IHC, WB. Anti-HCN3 mAb (GTX41987) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] CNGA4 is a modulatory subunit of vertebrate cyclic nucleotide-gated membrane channels that transduce odorant signals (Munger et al., 2001 [PubMed 11739959]).[supplied by OMIM, Mar 2008 ...
Complete information for CNGA1 gene (Protein Coding), Cyclic Nucleotide Gated Channel Alpha 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CNGB3 gene (Protein Coding), Cyclic Nucleotide Gated Channel Beta 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are responsible for the functional hyperpolarization-activated current (I(h)) in dorsal root ganglion (DRG) neurons. We studied HCN1-4 channel mRNA and protein expression and correlated these findings with I(h) functional properties in rat DRG neurons of different size. Quantitative RT-PCR (TaqMan) analysis demonstrated that HCN2 and HCN1 mRNAs were more abundantly expressed in large diameter (55-80 microm) neurons, while HCN3 mRNA was preferentially expressed in small diameter (20-30 microm) neurons. HCN4 mRNA expression was very low in neurons of all sizes. At the protein level, subunit-selective polyclonal antibodies and immunofluorescence indicated that HCN1 and HCN3 are present in large diameter neurons and small diameter neurons. Staining in small diameter neurons was in IB4-positive (non-peptidergic) and IB4-negative (peptidergic) cells. HCN2 immunofluorescent staining was heterogeneous and predominantly in large diameter ...
Spinal cord injury (SCI) leads to bereft voluntary control of bladder, but the possible role of spontaneous excited system in bladder of SCI patients is poorly understood. Hyper-polarization-activated cyclic nucleotide-gated (HCN) channels are deemed to regulate the spontaneous contraction of bladder, our study explored the functional role of HCN channels in SCI induced neurogenic bladder. Sixty female Sprague-Dawley rats were randomized into control, sham and SCI groups. Rat models subjected to SCI at S2 levels were successfully established and were assessed using hematoxylin and eosin staining and cystometry. In SCI rats, the mRNA and protein expression levels of HCN channels and the Ih density were significantly reduced, and expression levels of several bladder HCN1 channel regulatory proteins were also significantly changed. The effects of 50 µM forskolin and 50 µM 8-bromoadenosine 3,5-cyclic monophosphate on [Ca2+]i of isolated bladder interstitial cells of Cajal-like cells were ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinsons disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive β oscillations, and alleviation of motor deficits in ...
The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinsons disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive β oscillations, and alleviation of motor deficits in ...
Accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) upregulating its cell-surface expression and current density without affecting its voltage dependence and kinetics.
Hyperpolarization- and Cyclic Nucleotide-gated (HCN) channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. The HCN family consists of four members (HCN1-4). HCN channels represent the molecular correlates of I(h), a hyperpolarization-activated current best known for its role in controlling heart rate and in the regulation of neuronal resting membrane potential and excitability.. HCN channels are unique among vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization. HCN channels are encoded by four genes (HCN1-4) and are widely expressed throughout the heart and the central nervous system.. ...
Hyperpolarization-activated cyclic nucleotide-gated 1on channels (HCN) are gated by voltage, that is, they are able to detect changes in voltage and convert that into work for opening and closing (gating) the channel gate. The focus of this thesis was to investigate the gating mechanisms in HCN channels. Results from these experiments revealed that HCN channels have a voltage sensor (S4) similar to K v channels but have reversed gating. This makes up the first half of the thesis. In addition, the outward currents through HCN channels are susceptible to a voltage-dependent block by intracellular Mg2+. The experiments relating to the Mg2+ block make up the second half of the thesis. HCN channels mediate an inward cation current that contributes to spontaneous rhythmic firing activity in the heart and brain. These channels share homology with depolarization-activated Kv channels, including six transmembrane domains (S 1-S6) and a positively charged S4 segment. The S4 domain has been shown to function as
It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories. cAMP has three targets, protein kinase A (PKA), hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels, and exchange protein activated by cAMP (Epac). Studies have revealed that both PKA and HCN channels are important for long-term memory formation. However, little is known about the role of Epac in this process. Epac is a cAMP- dependent guanine nucleotide exchange factor for the small G proteins including Rap1.The Epac2 isoform is highly expressed in the forebrain. This dissertation examines the role of Epac in memory formation in several aspects. First, I show that activation of Epac within the hippocampus via intrahippocampal injection of Epac specific agonist 8-pCPT-2-O-Me-cAMP was able to enhance long-term memory formation in a PKA independent fashion. Next, I show that the levels of Rap1 activity, the direct target of Epac, increased during the memory formation.
KCNH channels are voltage-gated potassium channels with important physiological functions. In these channels, a C-terminal cytoplasmic region, known as the cyclic nucleotide binding homology (CNB-homology) domain displays strong sequence similarity to cyclic nucleotide binding (CNB) domains. However, the isolated domain does not bind cyclic nucleotides. Here, we report the X-ray structure of the CNB-homology domain from the mouse EAG1 channel. Through comparison with the recently determined structure of the CNB-homology domain from the zebrafish ELK (eag-like K(+)) channel and the CNB domains from the MlotiK1 and HCN (hyperpolarization-activated cyclic nucleotide-gated) potassium channels, we establish the structural features of CNB-homology domains that explain the low affinity for cyclic nucleotides. Our structure establishes that the self-liganded conformation, where two residues of the C-terminus of the domain are bound in an equivalent position to cyclic nucleotides in CNB domains, is a conserved
2Institute of Neuroscience, National Research Council, Cagliari, Italy. It is widely accepted that ligand-gated and voltage-dependent ion channels are crucial in mediating many of the central pharmacological and behavioral actions of ethanol (EtOH). Recent studies reported that the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels expressed in VTA neurons as well as hippocampal interneurons are modulated by EtOH, suggesting that they may represent an additional sensitive target for this drug. HCN channels are encoded by four HCN genes (HCN1-4), and their activation generates a typical inward current, termed Ih, which plays an important role in controlling neuronal resting membrane potential and firing rate of action potentials, and are heavily implicated in dendritic integration of post-synaptic potentials. Since HCN are highly expressed in CA3 glutamatergic pyramidal neurons, we have investigated the action of EtOH on Ih in these hippocampal cells from ...
Similar experiments were performed with cDNA derived from poly(A)+ RNA of bovine pineal tissue. Two overlapping fragments, harboring either the 5′ or 3′ part of the coding region for rod and cone CNG channels were amplified by two sets of primers similar to those used for amplification of fragments from chick cDNA.. Analysis of genomic structure of chick cone CNG channel. A chick genomic library in λFIXII-vector (Stratagene, La Jolla, Ca) was screened with two cDNA probes (F5′, nucleotides −39 to 926, and F3′, nucleotides 882 to 2391 of pCCG8B; Bönigk et al., 1993). Probe F5′ and F3′ yielded 12 and 7 positive signals, respectively. Two overlapping clones were chosen for further analysis. Clones were digested with SacI, XbaI, EcoRI,BamHI, SalI, and each possible combination of two endonucleases. Fragments were separated by agarose electrophoresis and those containing exon sequences were identified by Southern blotting using probes F5′ and F3′. These fragments were isolated and ...
In situ hybridization studies of mouse brain have revealed distinct but overlapping patterns of expression of HCN1 and HCN2 (Moosmang et al. 1999; Monteggia et al. 2000; Santoro et al. 2000). Single cell PCR studies provide additional strong evidence for coexpression of different HCN isoforms within single neurons (Franz et al. 2000). In particular, both HCN1 and HCN2 are prominently expressed in CA3 and CA1 pyramidal neurons of the hippocampus. Whole-cell patch-clamp recordings demonstrate a prominent Ih current with relatively rapid kinetics in CA1 pyramidal neurons. The presence of multiple HCN isoforms in a given cell raises the question as to whether the Ih current in these cells results from separate populations of homomeric channels or whether the different isoforms coassemble to form heteromultimeric channels.. By coexpressing HCN1 and HCN2 in Xenopus oocytes, we have provided several lines of functional evidence that the two isoforms can indeed coassemble to form functional ...
ID CN15C_MEDTR Reviewed; 703 AA. AC A0A072VMJ3; DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2014, sequence version 1. DT 25-OCT-2017, entry version 20. DE RecName: Full=Protein CNGC15c {ECO:0000303,PubMed:27230377}; DE AltName: Full=Cyclic nucleotide-gated ion channel protein 15 c {ECO:0000303,PubMed:27230377}; GN Name=CNGC15C {ECO:0000303,PubMed:27230377}; GN OrderedLocusNames=MTR_2g094860 {ECO:0000312,EnsemblPlants:KEH39345}; OS Medicago truncatula (Barrel medic) (Medicago tribuloides). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae; OC Pentapetalae; rosids; fabids; Fabales; Fabaceae; Papilionoideae; OC Trifolieae; Medicago. OX NCBI_TaxID=3880 {ECO:0000312,Proteomes:UP000002051}; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Jemalong A17; RX PubMed=22089132; DOI=10.1038/nature10625; RA Young N.D., Debelle F., Oldroyd G.E.D., Geurts R., Cannon S.B., RA Udvardi M.K., ...
ID A0A151R9I9_CAJCA Unreviewed; 418 AA. AC A0A151R9I9; DT 08-JUN-2016, integrated into UniProtKB/TrEMBL. DT 08-JUN-2016, sequence version 1. DT 25-OCT-2017, entry version 7. DE SubName: Full=Putative cyclic nucleotide-gated ion channel 19 {ECO:0000313,EMBL:KYP39025.1}; DE Flags: Fragment; GN ORFNames=KK1_039698 {ECO:0000313,EMBL:KYP39025.1}; OS Cajanus cajan (Pigeon pea) (Cajanus indicus). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae; OC Pentapetalae; rosids; fabids; Fabales; Fabaceae; Papilionoideae; OC Phaseoleae; Cajanus. OX NCBI_TaxID=3821 {ECO:0000313,EMBL:KYP39025.1, ECO:0000313,Proteomes:UP000075243}; RN [1] {ECO:0000313,EMBL:KYP39025.1, ECO:0000313,Proteomes:UP000075243} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Asha {ECO:0000313,Proteomes:UP000075243}; RX PubMed=22057054; DOI=10.1038/nbt.2022; RA Varshney R.K., Chen W., Li Y., Bharti A.K., Saxena R.K., RA Schlueter J.A., Donoghue ...
Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule cells (GCs) in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation. Using whole-cell recording in rat hippocampal slices, we investigated the net LTG effect on BC output. We showed that bath application of LTG significantly decreased the amplitude of evoked compound inhibitory postsynaptic currents (IPSCs) in GCs. In contrast, simultaneous paired recordings from BCs to GCs showed that LTG had no effect on both the amplitude and the paired-pulse ratio of the unitary IPSCs, suggesting that LTG did not
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A chronic compression of the DRG (CCD) produces cutaneous hyperalgesia and an enhanced excitability of neuronal somata in the compressed ganglion. The hyperpolarization-activated current (I(h)), present in the somata and axons of DRG neurons, acts to induce a depolarization after a hyperpolarizing event and, if upregulated after CCD, may contribute to enhanced neuronal excitability. Whole-cell patch-clamp recordings were obtained from acutely dissociated, retrogradely labeled, cutaneous, adult rat DRG neurons of medium size. Neurons were dissociated from L4 and L5 control DRGs or DRGs that had each been compressed for 5-7 d by L-shaped rods inserted into the intervertebral foramina. I(h), consisting of a slowly activating inward current during a step hyperpolarization, was recorded from every labeled, medium-sized neuron and was blocked by 1 mm cesium or 15 microm ZD7288. Compared with control, CCD increased the current density and rate of activation significantly without changing its reversal ...
HCN1 antibody [S70-28] (hyperpolarization-activated cyclic nucleotide-gated potassium channel 1) for IHC, IHC-Fr, IP, WB. Anti-HCN1 mAb (GTX41985) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
The backprojected volume was obtained from image processing of 2D crystal images of the potassium channel MloK1, via a novel software suite implemented in the 2dx and FOCUS software packages (http://focus-em.org). The PCO refined volume was obtained by applying projective constraint optimization to the backprojected volume.
CNGB1 Full-Length MS Protein Standard (NP_001129111), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene.
Neuropathic pain is induced by the injury to nervous systems and characterized by hyperalgesia, allodynia and spontaneous pain. The underlying mechanisms include peripheral and central sensitization resulted from neuronal hyperexcitability. A number of ion channels are considered to contribute to the neuronal hyperexcitability. Here, we particularly concentrate on an interesting ion channel, hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We overview its biophysical properties, physiological functions, followed by focusing on the current progress in the study of its role in the development of neuropathic pain. We attempt to provide a comprehensive review of the potential valuable target, HCN channels, in the treatment of neuropathic pain. ...
Hyperpolarization-activated cAMP-regulated (HCN) channels play important physiological roles in both cardiovascular and central nervous systems. Among the four HCN isoforms, HCN2 and HCN4 show high expression levels in the human heart, with HCN4 being the major cardiac isoform. Previously published crystal structure of mouse HCN2 (mHCN2) C-terminal fragment, including the C-linker and the cyclic-nucleotide binding domain (CNBD), has provided many insights into the cAMP-dependent gating in HCN channels. However, structures of other mammalian HCN channel isoforms have been lacking. Here we used a combination of approaches including structural biology, biochemistry, and electrophysiology, to study the cAMP-dependent gating in HCN4 channels. First we solved the crystal structure of the C-terminal fragment of human HCN4 (hHCN4) channel at 2.4A. Overall we observed a high similarity between mHCN2 and hHCN4 crystal structures. Functional comparison between two isoforms revealed that compared to mHCN2, ...
COMMENT Ih current - hyperpolarization-activated nonspecific Na and K channel - contributes to the resting membrane potential - controls the afterhyperpolarization Reference: 1. Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130, 1996. V1/2 = -84.1 mV k = 10.2 reversal potential = -32.9 +/- 1.1 mV at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms t2 = 1.04+/-0.16 s 2. Maccaferri, G. et al. Properties of the Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993. V1/2 = -97.9 mV k = 13.4 reversal potential = -18.3 mV 3. Pape, H.C. Queer current and pacemaker: The hyperpolarization-activated cation current in neurons, Annu. Rev. Physiol. 58:299-327, 1996. single channel conductance is around ...
COMMENT Ih current - hyperpolarization-activated nonspecific Na and K channel - contributes to the resting membrane potential - controls the afterhyperpolarization Reference: 1. Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130, 1996. V1/2 = -84.1 mV k = 10.2 reversal potential = -32.9 +/- 1.1 mV at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms t2 = 1.04+/-0.16 s 2. Maccaferri, G. et al. Properties of the Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993. V1/2 = -97.9 mV k = 13.4 reversal potential = -18.3 mV 3. Pape, H.C. Queer current and pacemaker: The hyperpolarization-activated cation current in neurons, Annu. Rev. Physiol. 58:299-327, 1996. single channel conductance is around ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...
Function of the hyperpolarization-activated inward rectification in nonmyelinated peripheral rat and human axons.: The function of time-dependent, hyperpolariza
The membrane protein encoded by this gene is a hyperpolarization-activated cation channel that contributes to the native pacemaker currents in heart and neurons. The encoded protein can homodimerize or heterodimerize with other pore-forming subunits to form a potassium channel. This channel may act as a receptor for sour tastes. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments ...
Gabapentin (GBP) is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2 and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+) or calretinin positive (CR+) inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100µM) caused a hyperpolarizing shift in the voltage of half activation (V1/2) thereby reducing the currents. GBP had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1
Like CNG channels, the HCN cation channels are members of the six-transmembrane superfamily (Kaupp and Seifert, 2001; Biel et al., 2002; Robinson and Siegelbaum, 2003). In contrast to most other voltage-gated channels, HCN channels open upon hyperpolarization and close at positive potential. The cyclic nucleotides cAMP and cGMP enhance HCN channel activity by shifting the activation curve of the channels to more positive voltages. The stimulatory effect of cyclic nucleotides does not depend on protein phosphorylation but is caused by direct interaction with the HCN channel protein. The current produced by HCN channels, termed Ih, If, or Iq, is found in a variety of excitable cells, including neurones, cardiac pacemaker cells, and photoreceptors (Pape, 1996; Robinson and Siegelbaum, 2003). The best-understood function of Ih is to control heart rate and rhythm by acting as pacemaker current in the sinoatrial (SA) node (Stieber et al., 2004). Ih is activated during the membrane hyperpolarization ...
Zatebradine Zatebradine(UL-FS49) is a potent HCN channels antagonist, which decreased the heartbeat in a reversible manner; 92% inhibition of the hHCN1-mediated current at 10 uM. ...
Bacteriophage phig1e Cng protein: a phage phi gle protein; amino acid sequence in first source; do not confuse with CNG channel (rod)
Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature, 452(7190), 1007- ...
Cyclic nucleotide-gated channels (CNGCs) are functional protein channels in the plasma membrane that have overlapping CaM ... binding sites transport divalent cations such as Ca2+. However, the exact role of the positioning of the CNGCs in this pathway ... The Ca2+ channels, such as the ryanodine receptor of the sarcoplasmic reticulum, can be inhibited by calmodulin bound to ... It does this by binding various targets in the cell including a large number of enzymes, ion channels, aquaporins and other ...
... increasing cyclic AMP (cAMP) concentration inside a cell, which then opens a cyclic nucleotide gated cation channel. The influx ... calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons". Nature. 368 (6471): 545-8. Bibcode: ... because Ca2+/calmodulin-dependent protein kinase II or CaMK activation directly represses the opening of cation channels, ... of Ca2+ ions through this channel triggers olfactory adaptation immediately ...
Cyclic nucleotide-gated channels: This superfamily of channels contains two families: the cyclic nucleotide-gated (CNG) ... Proton channels Voltage-gated proton channels Non-selective cation channels: These non-selectively allow many types of cations ... cyclic nucleotide-gated (HCN) channels. This grouping is functional rather than evolutionary. Cyclic nucleotide-gated channels ... Hyperpolarization-activated cyclic nucleotide-gated channels Temperature-gated channels: Members of the transient receptor ...
... channels belong to the superfamily of voltage-gated K+ (Kv) and cyclic nucleotide-gated (CNG) channels. HCN channels are ... channels are integral membrane proteins that serve as nonselective voltage-gated cation channels in the plasma membranes of ... by cyclic nucleotides (cAMP, cGMP, cCMP). Binding of cyclic nucleotides lowers the threshold potential of HCN channels, thus ... "Cyclic Nucleotide Regulated Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
It is still not known why the absence of cGMP-gated cation channels causes photoreceptor degradation. Mutations causing RP have ... Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel ... alpha 2 Cyclic nucleotide-gated channel alpha 3 Cyclic nucleotide-gated channel alpha 4 Cyclic nucleotide gated channel beta- ... Cyclic nucleotide-gated channel beta 1 Cyclic nucleotide-gated channel beta 3 The structure of the pore is similar to other ion ...
"A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous ... Known genetic causes of this are mutations in the cone cell cyclic nucleotide-gated ion channels CNGA3 (ACHM2) and CNGB3 (ACHM3 ... There are at least four genetic causes of congenital ACHM, two of which involve cyclic nucleotide-gated ion channels (ACHM2/ ... cGMP is particularly important in visual perception as its level controls the opening of cyclic nucleotide-gated ion channels ( ...
"Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels". Nature 452 (7190): 1007-11 ... "Cyclic Nucleotide-Regulated Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... Lolley RN, Lee RH (September 1990). "Cyclic GMP and photoreceptor function". The FASEB Journal : Official Publication of the ... 2006). "Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17". Curr. ...
... nucleotide cGMP was able to directly regulate a new assort of membrane channels now called the nucleotide-gated cation channels ... Cyclic guanosine monophosphate (cGMP) plays an important role in visual transductions. This fact was well rooted when Fesenko ...
A second strategy is to combine a cyclic nucleotide gated K+ channel with a photoactivated adenylyl cyclase to inhibit neuronal ... resulting in a pore which instead excluded cations in favor of anions. Other types of gated ion channels, ligand-gated and ... ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels ... Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion ...
... beta A1 Cyclic nucleotide-gated channel alpha 1 Cyclin A1 Cytochrome P450, family 1, member A1 Defensin, alpha 1 Dystrophin- ... alpha 1 Transient receptor potential cation channel, member A1 UDP glucuronosyltransferase 1 family, polypeptide A1 Urea ... alpha 1 Potassium large conductance calcium-activated channel, subfamily M, alpha 1 Proteasome (prosome, macropain) subunit, ...
In addition to NAADP gating the channel, there is evidence that the luminal pH also affects TPC channel activity, either TPC1 [ ... Cyclic ADP-ribose IP3 Clapper, David L.; Walseth, Timothy F.; Dargie, Peter J.; Lee, Hon Cheung (1987). "Pyridine Nucleotide ... These groups therefore concluded that TPCs were cation channels that conducted both Ca2+ and Na+ (analogous to the NMDA ... that TPCs function as NAADP-gated Ca2+-permeable channels, but it cannot be formally excluded that TPCs, acting as Na+ channels ...
The HCN channels were such a proposal; as they are cyclic nucleotide-gated channels. The two ion channels now suggested to ... Of these, transient receptor potential cation channel subfamily V member 1 (TRPV1) vanilloid receptors are responsible for the ... This G protein subunit activates a taste phosphodiesterase and decreases cyclic nucleotide levels. Further steps in the ... These second messengers may open gated ion channels or may cause release of internal calcium. Though all TAS2Rs are located in ...
cAMP, which is the second messenger here, opens a cyclic nucleotide-gated ion channel (CNG), producing an influx of cations ( ... The Ca2+ in turn opens a Ca2+-activated chloride channel, leading to efflux of Cl−, further depolarizing the cell and ... A calcium-calmodulin complex also acts to inhibit the binding of cAMP to the cAMP-dependent channel, thus contributing to ... This mechanism of transduction is somewhat unusual, in that cAMP works by directly binding to the ion channel rather than ...
... membrane receptors and hyperpolarization-activated cyclic-nucleotide-gated channels. For example, potassium channels and ... The most important cations for the action potential are sodium (Na+) and potassium (K+). Both of these are monovalent cations ... ligand-gated channels, and voltage-gated ion channels. For fixed ion concentrations and fixed values of ion channel conductance ... Voltage-gated ion channels, also known as voltage dependent ion channels, are channels whose permeability is influenced by the ...
Nakamura, Tadashi; Gold, Geoffrey H. (1987). "A cyclic nucleotide-gated conductance in olfactory receptor cilia". Nature. 325 ( ... Depolarization in these cells result from opening of non-selective cation channels upon binding of the odorant to the specific ... Salt and sour receptors are chemically gated ion channels, which depolarize the cell. Sweet, bitter, and umami receptors are ... Mechanosensitive ion channels are found in many cell types and it has been shown that the permeability of these channels to ...
... referred to as HCN channels (Hyperpolarization-activated cyclic nucleotide-gated). These channels open at very negative ... cation (positively charged ions) channels conduct more current as the membrane potential becomes more negative (hyperpolarised ... Another form of voltage-gated potassium channels are the delayed rectifier potassium channels. These channels carry potassium ... also known as voltage-gated ion channels) and can act to open or close the channel. The pore formed by an ion channel is ...
cGMP phosphodiesterase breaks down cGMP, an intracellular second messenger which opens cGMP-gated cation channels. ... Fung, BKK; Hurley, JB; Stryer, L (1981). "Flow of information in the light-triggered cyclic nucleotide cascade of vision". ... Decrease in cGMP concentration leads to decreased opening of cation channels and subsequently, hyperpolarization of the ... Kroll, S.; Phillips, W. J.; Cerione, R. A. (1989). "The regulation of the cyclic GMP phosphodiesterase by the GDP-bound form of ...
Cyclic nucleotide-gated channel alpha 4. *Cyclic nucleotide-gated ion channel. *Cyclic nucleotide gated channel beta 3 ... Transient receptor potential cation channel, member A1. *Transient receptor potential channel. *Transient receptor potential ... Cyclic nucleotide-gated channel alpha 1. *Cyclic nucleotide-gated channel alpha 2 ... Cyclic nucleotide-gated channel alpha 3. * ... Voltage-gated potassium channel database. *Voltage-gated proton ...
... trpc cation channels MeSH D12.776.543.585.400.901.555 - trpm cation channels MeSH D12.776.543.585.400.901.777 - trpp cation ... potassium channels, tandem pore domain MeSH D12.776.543.550.425.750.900 - potassium channels, voltage-gated MeSH D12.776. ... adenine nucleotide translocator 1 MeSH D12.776.543.585.450.162.235.200 - adenine nucleotide translocator 2 MeSH D12.776.543.585 ... cyclic amp MeSH D12.776.543.750.810.700 - receptors, purinergic p1 MeSH D12.776.543.750.810.700.100 - receptor, adenosine a1 ...
Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation ... cGMP keeps cGMP-gated channels open, allowing for the entry of calcium into the cell.[1] Like cAMP, cGMP is an important second ... Guanylate cyclase catalyzes the reaction of guanosine triphosphate (GTP) to 3',5'-cyclic guanosine monophosphate (cGMP) and ... a directly light-gated guanylate cyclase has been discovered in an aquatic fungus.[8][9] ...
cAMP, which is the second messenger here, opens a cyclic nucleotide-gated ion channel (CNG), producing an influx of cations ( ... The Ca2+ in turn opens a Ca2+-activated chloride channel, leading to efflux of Cl−, further depolarizing the cell and ... A calcium-calmodulin complex also acts to inhibit the binding of cAMP to the cAMP-dependent channel, thus contributing to ... This mechanism of transduction is somewhat unusual, in that cAMP works by directly binding to the ion channel rather than ...
... channels, nonselective cation channels, which play important roles in both visual and olfactory signal transduction. When ... Subunit of cyclic nucleotide-gated (CNG) channels, nonselective cation channels, which play important roles in both visual and ... Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGB1 subfamily. [View classification]Curated ... Note: In the rod cells, the CNGB1 locus encodes the cyclic nucleotide-gated cation channel beta-1 subunit and several glutamic- ...
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. ... intracellular cGMP activated cation channel activity Source: MGI. *intracellular cyclic nucleotide activated cation channel ...
Cyclic Nucleotide-Gated Cation Channels*Cyclic Nucleotide-Gated Cation Channels. *Cyclic Nucleotide Gated Cation Channels ... Cyclic Nucleotide-Gated Cation Channel*Cyclic Nucleotide-Gated Cation Channel. *Cyclic Nucleotide Gated Cation Channel ... Hyperpolarization Cyclic-Nucleotide Gated Ion Channels*Hyperpolarization Cyclic-Nucleotide Gated Ion Channels ... "Cyclic Nucleotide-Gated Cation Channels" by people in Harvard Catalyst Profiles by year, and whether "Cyclic Nucleotide-Gated ...
Arabidopsis thaliana cyclic nucleotide gated channel 3 forms a non-selective ion transporter involved in germination and cation ... Arabidopsis thaliana cyclic nucleotide gated channel 3 forms a non-selective ion transporter involved in germination and cation ...
Cyclic nucleotide-gated channels of rat olfactory receptor cells: divalent cations control the sensitivity to cAMP.. J W Lynch ... Cyclic nucleotide-gated channels of rat olfactory receptor cells: divalent cations control the sensitivity to cAMP. ... The results also indicate that divalent cation effects on cyclic nucleotide-gated channels may depend on the sequence of pre- ... Thus, the binding of divalent cations, probably via a regulatory protein, controls the sensitivity of the cAMP-gated channels ...
The presence of the cation channel, AtCNGC10, in root cap meristem cells, cell plate, and gravity-sensing columella cells, ... Patch clamp assays of an AtCNGC10-GFP fusion expressed in HEK293 cells measured significant cation currents. AtCNGC5 and ... maintain cation homeostasis essential for a wide range of physiological processes in plant cells. However, the precise ... suggest roles of AtCNGC10 in modulating cation balance required for root gravitropism, cell division and growth. ...
Expression of cyclic nucleotide-gated cation channels in airway epithelial cells. / Xu, W.; Leung, S.; Wright, J.; Guggino, S. ... Expression of cyclic nucleotide-gated cation channels in airway epithelial cells. Journal of Membrane Biology. 1999 Sep 15;171( ... Xu, W. ; Leung, S. ; Wright, J. ; Guggino, S. E. / Expression of cyclic nucleotide-gated cation channels in airway epithelial ... Xu, W., Leung, S., Wright, J., & Guggino, S. E. (1999). Expression of cyclic nucleotide-gated cation channels in airway ...
Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Mingyao Liu, Tsung-Yu Chen, Basheer ... Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. / Liu, Mingyao; Chen, Tsung-Yu; Ahamed, ... Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. In: Science. 1994 ; Vol. 266, No. 5189. ... Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science. 1994 Nov 25;266(5189):1348-1354 ...
Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels ... 2008). Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature, 452(7190), ... Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels ...
1.3.4 Cyclic nucleotide-gated channels With the cloning of the first cyclic nucleotide-gated channelfrombovine retina (Kaupp et ... 1.3.2 Calcium channels 15 1.3.3 Potassium channels 18 1.3.4 Cyclic nucleotide-gated channels 19 1.4 The bovine rod CNG channel ... channel subunit 26 1.4.4 Cloning of the second ((3) channel subunit 31 1.5 Cyclic nucleotide-gated channel antibodies 34 1.6 ... The cyclic nucleotide-gated (CNG) cation channel of rod photoreceptors plays an important role in the perception of light. The ...
... channel. Learn about this gene and related health conditions. ... of the cone photoreceptor cyclic nucleotide-gated (CNG) ... cone photoreceptor cGMP-gated cation channel beta-subunit. *cyclic nucleotide-gated cation channel modulatory subunit ... of the cone photoreceptor cyclic nucleotide-gated (CNG) channel. These channels are found exclusively in light-detecting ( ... cations) into cells. In cones, CNG channels remain open under dark conditions, allowing cations to flow in. When light enters ...
CNGA3 [600053], protein: cyclic nucleotide-gated cation channel, α3.. CNGB3 [605080], protein: cyclic nucleotide-gated cation ... GNAT2 [139340], protein: guanine nucleotide-binding protein, α-transducing activity polypeptide 2. ...
A family of hyperpolarization-activated mammalian cation channels.. Nature 393 587-91 1998 ... which belongs to the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel family. It is the major HCN channel ... Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (IPR030173). Short name: HCN4 ... HCN channels belong to the superfamily of voltage-gated pore loop channels. The voltage-dependent opening of the HCN channels ...
Cyclic nucleotide-gated cation channel α3 (CNGA3 or CNG3); photoreceptor cGMP-gated channel α-subunit. Also possibly expressed ... 4] "Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells." Distler M.et.al. 7532814. [5] " ... 6] "Subunit configuration of heteromeric cone cyclic nucleotide-gated channels." Peng C.et.al. 15134637. [7] "Total ... 12] "Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia." ...
Cyclic Nucleotide-Gated Cation Channels / genetics* * Dark Adaptation / physiology * Electroretinography * Female * Genetic ...
ed and cyclic nucleotide-gated (HCN) channels.. * pricing *. Z0292 α-Zearalanol ~98% (HPLC) * pricing ... Selective blocker of cation channel Ih; If blocker and sino-atrial node function modulator, blocks hyperpolarization-activat. ... HCN channel blocker: blocker of neuronal Ih, related cardiac If channels and ATP-sensitive Kir channels.. * pricing ... ZD0947 is potent ATP-sensitive K+ channels (KATP channels) opener. ZD0947 is an effective activator of smooth muscle-type KATP ...
1993) A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature 362:764-767. ... 1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science 266:1348-1354. ... 1997) β subunits of the olfactory cyclic nucleotide-gated channel form a nitric oxide activated Ca2+ channel. Neuron 18:951-958 ... 1997) Single-channel properties of ionic channels gated by cyclic nucleotides. Biophys J 72:1165-1181. ...
Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature 452, 1007-1011 (2008 ... These receptors function as ligand (odorant) gated, non-selective cation channels15,16. ORs are tetrameric complexes17 ... constitute a novel class of ligand gated ion channel15,17,18. Due to the lack of a relationship to the receptors and channels ... Insect olfactory receptors are heteromeric ligand-gated ion channels. Nature 452, 1002-1006 (2008). ...
... intracellular cGMP-activated cation channel activity (ortholog); intracellular cyclic nucleotide activated cation channel ... activity (ortholog); INVOLVED IN cation transport (ortholog); inorganic cation import across plasma membrane (ortholog); ion ... cyclic nucleotide gated channel alpha 3; cyclic nucleotide-gated cation channel alpha-3. ... cyclic nucleotide gated channel subunit alpha 3 Cnga3 cyclic nucleotide gated channel alpha 3 Symbol and/or name change. ...
Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. Nature, 452(7190), 1007- ...
... channel. Patients suffer from strongly impaired daylight vision, photophobia, nystagmus, and lack of color discrimination. We ... channel. Patients suffer from strongly impaired daylight vision, photophobia, nystagmus, and lack of color discrimination. We ... subunit of the cone photoreceptor cyclic nucleotide-gated (CNG) ... subunit of the cone photoreceptor cyclic nucleotide-gated (CNG ... cyclic nucleotide-gated cation channel α3; MIM 600053; ACHM2, MIM 216900) (Kohl et al., 1998), CNGB3 (cyclic nucleotide-gated ...
Cyclic Nucleotide-Gated Cation Channels / drug effects*. Dose-Response Relationship, Drug. Double-Blind Method. Drug ... 0/Cyclic Nucleotide-Gated Cation Channels; 155974-00-8/ivabradine From MEDLINE®/PubMed®, a database of the U.S. National ...
Cyclic Nucleotide-Gated Cation Channels); 0 (Intracellular Signaling Peptides and Proteins); 0 (cyclic GMP-binding protein); ... Endoplasmic reticulum (ER) Ca -channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel ... In particular, mice with cone cyclic nucleotide-gated (CNG) channel deficiency, a model for achromatopsia, display both early- ... This work investigated the role of Ca -release channels in ER stress, protein mislocalization, and cone death in a mouse model ...
... channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. In mammals, the HCN ... channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. The current produced by HC … ... Cyclic Nucleotide-Gated Cation Channels / genetics* * Cyclic Nucleotide-Gated Cation Channels / physiology* ... Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the ...
Cyclic Nucleotide Gated Channel Beta 1, including: function, proteins, disorders, pathways, orthologs, and expression. ... Subunit of cyclic nucleotide-gated (CNG) channels, nonselective cation channels, which play important roles in both visual and ... Subunit of cyclic nucleotide-gated (CNG) channels, nonselective cation channels, which play important roles in both visual and ... A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. (PMID: 7682292) Chen TY … Yau KW (Nature 1993) 3 4 ...
cone photoreceptor cGMP-gated cation channel beta-subunit. *cyclic nucleotide-gated cation channel modulatory subunit ... cyclic nucleotide gated channel beta 3. Enable Javascript to view the expand/collapse boxes.. Printable PDF Open All Close All ... of the cone photoreceptor cyclic nucleotide-gated (CNG) channel. These channels are found exclusively in light-detecting ( ... cations) into cells. In cones, CNG channels remain open under dark conditions, allowing cations to flow in. When light enters ...
hyperpolarization activated; cyclic nucleotide-gated; cation-channel; HCN; in situ hybridization; Ih; If; cyclic nucleotide ... Here a cDNA was identified which codes for the "murine hyperpolarization-activated cyclic nucleotide-gated cation channel 1" ( ... "murine hyperpolarization-activated cyclic nucleotide-gated cation channel 1" (mHCN1) codiert. Das Genprodukt weist alle ... Characterization and Tissue-Distribution of the murine Hyperpolarization-Activated Cyclic Nucleotide-Gated Cation Channel mHCN1 ...
1993) A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature 362:764-767. ... 1994) Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells. Neuropharmacology 33:1275-1282. ... 1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science 266:1348-1354. ... 1992) Molecular cloning and single-channel properties of the cyclic nucleotide-gated channel from catfish olfactory neurons. ...
Cyclic Nucleotide Gated Channel Alpha 1, including: function, proteins, disorders, pathways, orthologs, and expression. ... intracellular cyclic nucleotide activated cation channel activity. IEA. --. GO:0005249. voltage-gated potassium channel ... Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA1 subfamily. ... Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA1 subfamily. ...
intracellular cAMP-activated cation channel activity IEA. UniProtKB:Q9UL51, ensembl:ENSP00000251287. 14298760. Ensembl. GO_REF: ... cyclic nucleotide-gated K+ 2) MGI Alliance Rattus norvegicus (Norway rat) : Hcn2 (hyperpolarization activated cyclic nucleotide ... hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2. Description:. ENCODES a protein that ... HCN2 (hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2). HGNC. Ensembl, NCBI, OrthoDB. ...
  • 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)
  • 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)
  • 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)
  • Along with another protein, the encoded protein forms a cGMP-gated cation channel in the plasma membrane, allowing depolarization of rod photoreceptors. (genecards.org)
  • CNGA1 (Cyclic Nucleotide Gated Channel Alpha 1) is a Protein Coding gene. (genecards.org)
  • This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. (genecards.org)
  • 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)
  • The protein exhibits all essential properties of an I h -channel. (tum.de)
  • 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)
  • Aiba, H. , Fujimoto, S. , Ozaki, N. 1982 Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP receptor protein. (wiley.com)
  • 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)
  • 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)
  • 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)
  • The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K + channels, particularly in the pore region. (sciencemag.org)
  • This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. (genetex.com)
  • Made up of glycoproteins, or proteins with sugar molecules attached, pacemaker channels -- also known as HCN channels (Hyperpolarization activated, Cyclic Nucleotide-gated cation channels) -- allow the entrance of sodium ions into the cell based on the configuration of the protein. (bio-medicine.org)
  • Along the nephron, natriuretic and diuretic actions of ANP are mediated by inhibiting the basolaterally expressed Na + -K + -ATPase, reducing apical sodium, potassium, and protein organic cation transporter in the proximal tubule, and decreasing Na + -K + -2Cl − cotransporter activity and renal concentration efficiency in the thick ascending limb. (physiology.org)
  • 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)
  • 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)
  • 2] "The Arabidopsis dnd1 'defense, no death' gene encodes a mutated cyclic nucleotide-gated ion channel. (tcdb.org)
  • 5] "Characterisation of calmodulin binding to cyclic nucleotide-gated ion channels from Arabidopsis thaliana. (tcdb.org)
  • 6] "Developmentally regulated expression of a cyclic nucleotide-gated ion channel from Arabidopsis indicates its involvement in programmed cell death. (tcdb.org)
  • 7] "Phylogenetic relationships within cation transporter families of Arabidopsis. (tcdb.org)
  • 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)
  • Subunit of cyclic nucleotide-gated (CNG) channels, nonselective cation channels, which play important roles in both visual and olfactory signal transduction. (uniprot.org)
  • CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. (wikipedia.org)
  • CNGCs, nonselective cation channels that open upon cyclic nucleotide binding, are particularly important in the olfactory and visual systems ( 3 ). (sciencemag.org)
  • 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)
  • A CNG channel consists of four subunits around a central pore. (wikipedia.org)
  • Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel alpha 2 Cyclic nucleotide-gated channel alpha 3 Cyclic nucleotide-gated channel alpha 4 Cyclic nucleotide gated channel beta-subunits include: Cyclic nucleotide-gated channel beta 1 Cyclic nucleotide-gated channel beta 3 The structure of the pore is similar to other ion channels that contain P-loops. (wikipedia.org)
  • 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)
  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. (nih.gov)
  • 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)
  • 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)
  • That is, affinity of blocking agents for the pore of ion channels varies with membrane voltage. (upenn.edu)
  • The human HCN4 gene encodes the pore-forming subunit of a hyperpolarization-activated, cyclic nucleotide-modulated cation channel. (creativebiomart.net)
  • 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)
  • Potassium channels use diverse mechanisms of gating (the processes by which the pore opens and closes), but they all exhibit very similar ion permeability characteristics ( 1 ). (sciencemag.org)
  • Because of these properties, K + channels are classified as "long pore channels," invoking the notion that multiple ions queue inside a long, narrow pore in single file. (sciencemag.org)
  • Molecular cloning and mutagenesis experiments have reinforced the conclusion that all K + channels have essentially the same pore constitution. (sciencemag.org)
  • How can these two essential features of the K + channel pore be reconciled? (sciencemag.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)
  • In this study, we investigate the molecular determinants and mechanisms of ion permeation and ion charge selectivity in this family of channels by characterizing the single channel conductance and rectification of α1 homomeric human glycine receptor channels (GlyRs) containing pore mutations that impart cation selectivity. (rupress.org)
  • Mean outward conductances in the SDM+R19'A and SDM+R19'E GlyRs were increased when internal divalent cations were absent, consistent with the intracellular end of the pore being flanked by fixed negative charges. (rupress.org)
  • These results also further confirm the role of external pore vestibule electrostatics in determining the conductance and rectification properties of the ligand-gated ion channels. (rupress.org)
  • After the identification of amino acids from purified proteins, cloning and functional expression of CNG channels were performed. (wikipedia.org)
  • A Cyclic nucleotide-binding domain is an intracellular domain located in the C-terminus region and has a similar sequence to other cyclic nucleotide-binding proteins. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • To analyze the assembly of TRPV subunits in living cells, we generated fluorescent fusion proteins or FLAG-tagged TRPV channel subunits. (biologists.org)
  • Potassium ions diffuse rapidly across cell membranes through proteins called K + channels. (sciencemag.org)
  • 10] "Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit. (tcdb.org)
  • 12] "Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia. (tcdb.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)
  • 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)
  • Calcium, calmodulin, and phosphorylation modulate the opening of CNG channels. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Their function can be the result of a combination of the binding of cyclic nucleotides (cGMP and cAMP) and either a depolarization or a hyperpolarization event. (wikipedia.org)
  • A family of hyperpolarization-activated mammalian cation channels. (ebi.ac.uk)
  • 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)
  • 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)
  • HCN1 includes Hyperpolarization-activated cation channels of the HCN gene family, which contribute to spontaneous rhythmic activity in both heart and brain. (thermofisher.com)
  • HCN1 is a member of a family of pacemaker channels activated by hyperpolarization and regulated by cyclic nucleotides. (thermofisher.com)
  • 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)
  • 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)
  • 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)
  • A key component of the membrane clock is an inward depolarizing cation current that is activated in early diastole by hyperpolarization, known as the "funny current" or I f ( 10,11 ). (onlinejacc.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)
  • 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)
  • 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)
  • As a result, the CNG channel closes, stopping the dark current and producing a membrane hyperpolarization as the electrical response to light, which reduces the synaptic-transmitter release in darkness. (jhu.edu)
  • I used the hyperpolarization-activated and cyclic nucleotide-gated cation channels (HCN channels), which are a key determinant of the intrinsic properties of auditory brainstem neurons, as a target to study the influence of auditory experience on the intrinsic properties of neurons in the auditory brainstem. (uni-muenchen.de)
  • 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)
  • 7] "Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. (tcdb.org)
  • In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. (genecards.org)
  • 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)
  • Photoreceptor channels strongly discriminate between cGMP and cAMP, whereas the olfactory channel is almost equally sensitive to both ligands. (aspetjournals.org)
  • 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)
  • In darkness, the cyclic nucelotide, guanosine 3':5'-cyclic monophosphate (cGMP), directly activates a cyclic-nucleotide-gated (CNG) cation channel on the photoreceptor plasma membrane and maintains a steady inward electrical current across the membrane, depolariziang the cell and maintaining a steady release of the neurotransmitter glutamate from the cell's synaptic terminal. (jhu.edu)
  • 11] "Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. (tcdb.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)
  • A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate. (inta.cl)
  • 9-12 CNG channels are activated by cAMP and cGMP, 13 the levels of which are elevated when endothelial cells are exposed to adenosine. (ahajournals.org)
  • Increase in cAMP and cGMP concentration activates cyclic nucleotide gated channels (CNGC), which causes influx of Ca 2+ into the cytosol. (els.net)
  • Ali R, Zielinski RE and Berkowitz GA (2006) Expression of plant cyclic nucleotide‐gated cation channels in yeast. (els.net)
  • 1] "Cloning and first functional characterization of a plant cyclic nucleotide-gated cation channel. (tcdb.org)
  • Both types of subunits are members of the six-transmembrane segment channel superfamily. (aspetjournals.org)
  • 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)
  • 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)
  • Members of the ligand-gated ion channel superfamily mediate fast synaptic transmission in the nervous system. (rupress.org)
  • HCN channels exhibit weak selectivity for potassium over sodium ions. (ebi.ac.uk)
  • 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)
  • We studied the selectivity and promiscuity of homo- and heteromultimerization between TRPV channel subunits in living cells. (biologists.org)
  • Main chain carbonyl oxygen atoms from the K + channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K + ions but not smaller Na + ions. (sciencemag.org)
  • The characterization of distinct δ-ENaC splice variants may explain the diverse cation selectivity and amiloride sensitivity of native ENaC in the lung. (physiology.org)
  • 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)
  • 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)
  • GO annotations related to this gene include ion channel activity and cGMP binding . (genecards.org)
  • Analysis of the chick cone CNG channel gene reveals that these forms are produced by alternative splicing, which removes either one or two exons from the transcript. (jneurosci.org)
  • This exon is missing in the gene for the rod CNG channel α-subunit. (jneurosci.org)
  • The HCN4 gene provides instructions for making a channel that transports positively charged atoms (ions) into heart muscle cells. (medlineplus.gov)
  • This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. (genscript.com)
  • 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)
  • The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. (genscript.com)
  • The retinal rod cGMP-gated cation channel is a hetero-oligomer composed of the alpha subunit Cnga1 and a beta subunit. (lsbio.com)
  • b) Structure of the cytoplasmic domain from a single subunit of HCN2 channels (PDB: 1Q5O). (els.net)
  • 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)
  • 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)
  • 6] "Subunit configuration of heteromeric cone cyclic nucleotide-gated channels. (tcdb.org)
  • Therefore, GAF and CNB domains have evolved independently to bind cyclic nucleotides. (biomedcentral.com)
  • This entry represents HCN4, which belongs to the hyperpolarisation-activated cyclic nucleotide-gated (HCN) channel family. (ebi.ac.uk)
  • The HCN4 channel allows potassium and sodium ions to flow into cells of the SA node. (medlineplus.gov)
  • 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)
  • 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)
  • Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain. (ebi.ac.uk)
  • In mammals, the HCN channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. (nih.gov)
  • 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)
  • Cyclic nucleotide-gated (CNG) channels play central roles in visual and olfactory signal transduction. (jneurosci.org)
  • Cnga1 is the alpha 1 subunit of cyclic nucleotide-gated (CNG) cation channels involved in visual and olfactory signal transduction. (lsbio.com)
  • Molecular cloning allowed for the discovery of similar channels in many other tissues. (wikipedia.org)
  • In 2000, scientists performed studies using mouse retina and molecular cloning to find a new subunit of the channel, CNG6. (wikipedia.org)
  • Molecular characterization of the cyclic nucleotide-gated. (ubc.ca)
  • 1989) of what is now known to be the CNG channel α subunit facilitated its molecular characterization. (ubc.ca)
  • A heterologous expression system was developed to examine molecular aspects of the α and β subunits of the CNG channel. (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)
  • 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)
  • Two molecular mechanisms are crucial for the proper physiological function of retinal CNG channels. (upenn.edu)
  • Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. (springer.com)
  • 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)
  • Drosophila odorant receptors are both ligand-gated and cyclic-nucleotide-activated cation channels. (wikipedia.org)
  • Interestingly, while genes involved in immune system function were down-regulated in the brains of mature males, changes in the expression levels of several receptors and channels were observed suggesting that some rewiring is occurring in the brain at sexual maturity. (biomedcentral.com)
  • CNG channels have also been found to exist in prokaryotes, including many spirochaeta, though their precise role in bacterial physiology remains unknown. (wikipedia.org)
  • We also discuss in detail the different aspects of HCN channel physiology in the heart and nervous system. (nih.gov)
  • Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3. (uniprot.org)
  • 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)
  • We present the biophysical investigation of the mechanism underlying voltage sensitivity of ion channel block. (upenn.edu)
  • 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)
  • 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)
  • 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)
  • Potassium channels also share a constellation of permeability characteristics that is indicative of a multi-ion conduction mechanism: The flux of ions in one direction shows high-order coupling to flux in the opposite direction, and ionic mixtures result in anomalous conduction behavior ( 2 ). (sciencemag.org)
  • CNG channels can be activated by cAMP or cGMP exclusively, or sometimes by a combination of both cNMPs, and some channels are more selective than others. (wikipedia.org)
  • 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)
  • These channels are non-selective for cations and open upon cGMP binding. (upenn.edu)
  • Gap junction channels exhibit connexin dependent biophysical properties, including selective intercellular passage of larger solutes, such as second messengers and siRNA. (nih.gov)
  • All three homotypic channels are poorly selective toward monovalent cations as illustrated by the Na+/K+ conductance ratios. (nih.gov)
  • Second, how can K + channels be so highly selective and at the same time, apparently paradoxically, exhibit a throughput rate approaching the diffusion limit? (sciencemag.org)
  • Classically, there are two families of ENaC characterized in the lung, the first of which are highly selective cation (HSC) channels that transport Na + unidirectionally with low conductances of ∼6 pS. (physiology.org)
  • CNG channels are ion channels regulated by the direct binding of cyclic nucleotides. (els.net)
  • The direct binding of cyclic AMP upon adrenaline release also enhances channel opening, leading to an increased frequency of action potential. (ubc.ca)
  • RT "Nuclear-localized cyclic nucleotide-gated channels mediate symbiotic RT calcium oscillations. (genome.jp)
  • 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)
  • Cyclic nucleotide-gated (CNG) channels mediate the transduction of light signals to electrical signals in vertebrate photoreceptors. (upenn.edu)
  • The vanilloid receptor-related TRP channels (TRPV1-6) mediate thermosensation, pain perception and epithelial Ca 2+ entry. (biologists.org)
  • The ligand-gated ion channels (LGICs) * mediate fast synaptic transmission in the central and peripheral nervous system. (rupress.org)
  • There is a cyclic nucleotide binding domain (CNBD) and connection region to the S6 segment in the carboxy terminal. (wikipedia.org)
  • In the C terminus the channels carry a cyclic nucleotide-binding domain (CNBD) [ PMID: 12161074 ]. (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)
  • In the cytosolic C terminus, CNG channel subunits carry a cyclic nucleotide-binding domain (CNBD) that serves as activation domain. (aspetjournals.org)
  • One of these mutants, suppressor S58 possesses a single amino acid substitution, arginine 557 to cysteine, in the αC-helix of the cyclic nucleotide-binding domain (CNBD). (pubmedcentralcanada.ca)
  • In silico modelling and site-directed mutagenesis analyses suggest that arginine 557 in the αC-helix of the CNBD is important for channel regulation, but not for basic function. (pubmedcentralcanada.ca)
  • 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)
  • Cyclic nucleotide-gated (CNG) channels are crucial for sensory transduction in rod and cone photoreceptors and olfactory sensory neurons. (rupress.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)
  • 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)
  • It is believed that hundreds of different types of ion channels exist in the body, each with a distinct responsibility for sending a specific message, and that specific pacemaker channels exist in peripheral nerves as well as in the heart and the central nervous system. (bio-medicine.org)
  • In the heart, for instance, signals generated by pacemaker channels stimulate the heart muscle to contract, and in the brain, they control sleep and waking. (bio-medicine.org)
  • We think we have only scratched the surface in this area, as pacemaker channels may also play a role in inflammatory pain as well as other types, " said Dr. Wickenden. (bio-medicine.org)
  • To regulate intracellular cation homeostasis, plants have evolved several distinct classes of transporters to facilitate the movement of monovalent and divalent cations across cellular membranes. (biomedcentral.com)
  • CNG channels pass monovalent cations, such as Na + and K + , but do not discriminate between them. (aspetjournals.org)
  • It always involves more than one amino acid and includes all residues involved in nucleotide-binding. (uniprot.org)
  • The results also point to the amino-terminal part of the olfactory channel as an element for gating, which may have general significance in the operation of ion channels with similar overall structures. (elsevier.com)
  • displaying little or no endogenous amino acid-gated channel activity ( Zhang and Huganir, 1999 ). (plantphysiol.org)
  • Without exception, all contain a critical amino acid sequence, the K + channel signature sequence. (sciencemag.org)
  • The amino acid sequence of the K + channel from Streptomyces lividans (KcsA K + channel) ( 5 ) is similar to that of other K + channels, including vertebrate and invertebrate voltage-dependent K + channels, vertebrate inward rectifier and Ca 2+ -activated K + channels, K + channels from plants and bacteria, and cyclic nucleotide-gated cation channels (Fig. 1 ). (sciencemag.org)
  • Expression in mammalian cells helped resolve confusion regarding the JVL of the rod CNG channel a subunit. (ubc.ca)
  • 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)
  • The discovery of CNG channels is related to the discovery of intracellular messengers responsible for the mediation of responses in retinal photoreceptors. (wikipedia.org)
  • Cyclic nucleotides are ubiquitous intracellular messengers. (biomedcentral.com)
  • 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)
  • Exogenous expression of α subunits alone generates functional CNG channels in oocytes. (rupress.org)
  • 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 basic neuronal projections and the intrinsic properties of neurons, such as the expression of specific ion channels, are already established and adjusted in the SOC during the perinatal period of partial deafness. (uni-muenchen.de)
  • 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)
  • 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)
  • In the medullary collecting duct, ANP reduces sodium reabsorption by inhibiting the cyclic nucleotide-gated cation channels, the epithelial sodium channel, and the heteromeric channel transient receptor potential-vanilloid 4 and -polycystin 2 and diminishes vasopressin-induced water reabsorption. (physiology.org)
  • This binding reduces the effective affinity of the channel for cyclic nucleotides, apparently by acting on channel gating, which is tightly coupled to ligand binding. (elsevier.com)
  • Ligand-binding domain subregions contributing to bimodal agonism in cyclic nucleotide-gated channels. (nih.gov)
  • Cyclic nucleotide-gated (CNG) channels bind cGMP or cAMP in a cytoplasmic ligand-binding domain (BD), and this binding typically increases channel open probability (P(o)) without inducing desensitization. (nih.gov)
  • There are two general gating mechanisms of cation channels: ligand gating and voltage gating. (utsouthwestern.edu)
  • 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)
  • Ligand-gated channels are diverse with respect to ligands that cause them 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)
  • 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)
  • BK channels) contain a conserved, C-terminal ligand-binding domain that we call the RCK domain, for regulation of K + conductance. (utsouthwestern.edu)
  • The research in my lab is to understand the mechanisms of ligand-dependent gating in K + channels opened by RCK domains. (utsouthwestern.edu)
  • The extent of ligand discrimination varies significantly between the individual CNG channel types. (aspetjournals.org)
  • 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)
  • Cyclic nucleotides are small ligands used to control the gating of CNG channels. (els.net)
  • Calcium signals are generated through the coordinated action of calcium influx channels and calcium efflux transporters. (els.net)
  • 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)
  • 8] "A cyclic nucleotide-gated ion channel, CNGC2, is crucial for plant development and adaptation to calcium stress. (tcdb.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)
  • A feature of olfactory transduction not shared by vision, however, is the presence of a calcium-activated chloride channel that helps amplify the transduced sensory signal. (jhu.edu)
  • Voltage-gated calcium (Ca V ) channels have a similar structure ( Fig. 1 ). (aspetjournals.org)
  • CNG channels were also found in cone photoreceptors, chemo sensitive cilia of olfactory sensory neurons, and the pineal gland. (wikipedia.org)
  • 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)
  • 1 ) identification of nonphagocytic NADPH oxidases as sources of regulated reactive species (RS) production in epithelia, 2 ) an understanding that excessive treatment with antioxidants can result in greater oxidative stress, and 3 ) characterization of novel RS signaling pathways that converge upon ion channel regulation. (physiology.org)
  • 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)
  • The expressed a subunit reconstituted alone did not generate functional cGMP-gated channels. (ubc.ca)
  • Reconstitution of the heterologously expressed channel complex comprising the 80 kDa α and complete β subunits generated functional channels. (ubc.ca)
  • The shorter splice variant is functional when heterologously expressed, and it is approximately twofold more sensitive to activation by cGMP than the cone CNG channel. (jneurosci.org)
  • This review will mainly focus on recent insights into the functional role of the channels apart from their classic role as pacemakers. (mdpi.com)
  • Dr. Chen is now a Professor in the Department of Neurology and runs an ion channel structural/functional laboratory at the Center for Neuroscience. (ucdavis.edu)
  • Research in Dr. Chen's laboratory focuses on understanding the structural and functional mechanisms of ion channels. (ucdavis.edu)
  • The structures will provide a snapshot of the opened and closed states, but the functional work will provide information on the energetics of the gating process. (utsouthwestern.edu)
  • Ruta V, Y Jiang, A Lee, J Chenand R MacKinnon (2003) Functional analysis of an archaebacterial voltage-dependent K+ channel . (utsouthwestern.edu)
  • In contrast, β subunits do not form functional channels when expressed alone. (rupress.org)
  • By comparing our binding data to functional measurements of potency in full-length channels containing the same single substitutions, we found that two residues, L633 and I636, reduced potency more severely than affinity when mutated, and proposed that these residues are involved in a post-binding transition event. (ubc.ca)
  • This likely reflects a decrease in its ability to form a gating ring in the intact channel and explains the reported inhibition of opening by thismutation.The work presented in this thesis demonstrates the value of studying the C-terminus of the HCN channel in isolation to uncover the mechanism by which the HCN C-terminus and cAMP binding control channel opening that would otherwise be hidden by functional experiments. (ubc.ca)
  • CNGalpha1-3 are able to form functional homooligomeric channels which control the flow of Na+ and Ca2+ into the outer segment of photoreceptor cells in response to light-induced changes in cGMP concentrations. (lsbio.com)
  • Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. (embl.de)
  • To find BD residues responsible for con action or low pro-action efficacy or both, we constructed chimeric CNG channels: subregions of the fCNGA2 BD were substituted with corresponding sequence from the rat CNGA4 BD, which does not support con action. (nih.gov)
  • The purpose here is to provide a contemporary overview of the state-of-the science related to redox regulation of lung epithelial channels and transporters in health and disease. (physiology.org)
  • In the lung, amiloride-sensitive epithelial Na + channels (ENaC), composed of α-, β-, and γ-subunits, have been identified as the major contributor of net salt and water reabsorption. (physiology.org)
  • 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)
  • 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)
  • 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)