TY - JOUR. T1 - Cyclic nucleotide-gated cation channel expression in embryonic chick brain. AU - Timpe, Leslie C.. AU - Jin, Kun Lin. AU - Puelles, Luis. AU - Rubenstein, John L.R.. N1 - Funding Information: We thank Brian Williams, PhD, for his advice and Ms. Katherine A. Logee for technical support. This work was supported by NIH Grant PO1 HL43821 and the Dept. of Veterans Affairs.. PY - 1999/3/20. Y1 - 1999/3/20. N2 - Cyclic nucleotide-gated cation channels mediate sensory transduction in vertebrate photoreceptors and olfactory epithelium. These channels are also present in some non-sensory cells, but little is known of their physiOlOgiCal roles outside sensory systems. Using in situ hybridization we found that cyclic nucleotide channel mRNA is expressed specifically in the embryonic chicken forebrain, thalamus, optic tectum, basal midbrain and hindbrain, as well as in the branchial arches, limb buds and skin. Cyclic nucleotide gated channels may thus contribute to development or to cellular ...

Second messenger, cAMP, causes the opening of cation-selective cyclic nucleotide-gated (CNG) channels and depolarization of the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory subunit of this channel which is known to play a central role in the transduction of odorant signals and subsequent adaptation. By accelerating the calcium-mediated negative feedback in olfactory signaling it allows rapid adaptation to odor stimulation and extends its range of odor detection (By similarity).

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the HCN4 gene. There are four HCN channels. HCN4 is prominently expressed in the pace maker region of the mammalian heart. Some humans with bradycardia and Sick sinus syndrome have been shown to have mutations in their HCN4 gene. The role of HCN channels in autonomic control of heart rate is currently a matter of ongoing investigation. HCN4 has been shown to interact with HCN2. Cyclic nucleotide-gated ion channel Funny current GRCh38: Ensembl release 89: ENSG00000138622 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000032338 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M (May 1999). Two pacemaker channels from human heart with profoundly different activation kinetics. The EMBO Journal. 18 (9): 2323-9. doi:10.1093/emboj/18.9.2323. PMC 1171315 . PMID 10228147. Seifert R, Scholten A, ...

The HCN channels form the subgroup of cyclic nucleotide-gated cation channel within the large superfamily of the pore loop cation channels. Like other pore loop channels, HCN channels are complexes consisting of 4 subunits that are arranged around the ventral pore. Each HCN channe subunit consists of 3 principal structural ovules: the transmembrane core and the cystosolic amino (N) terminal and carboxyl © terminal domains. The transmembrane core is comosed of 6 transmembrane segments (S1-S6) including a positively charged voltage sensor (S4) and the ion conducting pore region between (S5 and S6. The proximal portion of the systolic C-terminal domain contains the cyclic nucleotide binding domain (CNBD), which mediates modulation by cyclic nucleotides. A highly conserved asparagine residue in the extracellular loop between S5 and the pore loop is glycosylated; this posttranstional channel modification is crucial for normal cell surface expression [1690]. ...

Cyclic nucleotide-gated (CNG) channels mediate the transduction of light signals to electrical signals in vertebrate photoreceptors. These channels are non-selective for cations and open upon cGMP binding. The intracellular cGMP concentration is elevated in darkness, and the current through CNG channels maintains the membrane of the rod photoreceptor at around -40 mV. When light enters the retina, it triggers a signal transduction cascade that decreases intracellular cGMP, and therefore CNG channels close. A reduction in CNG current hyperpolarizes the rod. Two molecular mechanisms are crucial for the proper physiological function of retinal CNG channels. First, block of these channels by physiological agents reduces membrane noise in rods. This feature enables rods to detect photons with high sensitivity. Second, CNG channels must be able to conduct current in response to the light-triggered changes in intracellular cGMP. In other words, they should open and close gradually in response to cGMP

Cyclic nucleotide-gated (CNG)1 ion channels are key players in visual and olfactory signal transduction pathways (reviewed in Lancet, 1986; Yau and Baylor, 1989; Zufall et al., 1994). Although they are only weakly voltage dependent, CNG channels have regions of sequence similarity with voltage-gated channels (Jan and Jan, 1990). One region of high conservation between CNG channels and voltage-gated channels is the P region, thought to line a portion of the ion-conducting pore. Shaker K+ channels that have had portions of their P region replaced with the corresponding region from CNG channels take on many of the permeation properties of CNG channels (Heginbotham et al., 1992). These chimeric channels become permeable to Na+ as well as to K+ and become blocked by the divalent cations Mg2+ and Ca2+. Like voltage-gated channels, CNG channels are thought to possess multi-ion pores (Furman and Tanaka, 1990; Sesti et al., 1995). The external divalent cation binding site is thought to involve the E363 ...

Ca2+ signaling is central to many aspects of plant physiology; however, the channels involved in mediating Ca2+ fluxes in plants remain largely elusive. This is at least partially due to the absence of plant homologs to many of the well-characterized Ca2+ channels present in animals. Instead, plants have expanded families of ligand-gated, non-specific cation channels such as the cyclic nucleotide-gated channels (CNGCs) and glutamate receptor-like channels (GLRs), which are hypothesized to provide Ca2+ channel function in plants. The 20 member CNGC family represents one of two large families of putative Ca2+ channels in Arabidopsis, and various isoforms have been implicated in plant development and stress-response signaling, including immunity. Among Arabidopsis CNGC mutants, cpr22 and dnd1 are the best characterized mutants that show similar autoimmunity phenotypes such as constitutive expression of PR genes and heightened accumulation of salicylic acid. To understand the regulation of plant ...

Dr. Chen earned his medical degree at National Yang-Ming University in 1986 in Taiwan and his Ph.D. at Johns Hopkins University Medical School in 1994. He then received postdoctoral training at Brandeis University (1994-1996) and spent 4 years (1996-2000) as teaching faculty at National Yang-Ming University before joining UC Davis in 2001.. During his graduate studies at Hopkins, Dr. Chen worked under Professor King-Wai Yau in the Department of Neuroscience. He discovered calmodulin modulation of cyclic nucleotide-gated cation channels critical in visual and olfactory sensory adaptation mechanisms. The discovery opened the field of calmodulin modulation of ion channels.. During his postdoctoral training at Brandeis, Dr. Chen examined the biophysical mechanism of CLC chloride channels. Since then, Dr. Chen has been well known in the field of chloride channels. He received Paul Cranefield award from Society for General Physiologists in 2004. His laboratory currently studies various ion channels, ...

Additional file 5: of A comparison of heat-stress transcriptome changes between wild-type Arabidopsis pollen and a heat-sensitive mutant harboring a knockout of cyclic nucleotide-gated cation channel 16 (cngc16)

Xi-Qin Deng, Associate Professor of Cell Biology, and the Joanne I Moore Professor of Pharmacology at University of Oklahoma Health Sciences Center will be delivering a seminar on cGMP/PKG signaling regulation of endoplasmic reticulum homeostasis in CNG channel deficiency on Wednesday, January 24th at 12:00 Noon in the Moran Eye Center auditorium.. Abstract: Mutations in the CNGA3 and CNGB3 genes that encode the cone cyclic nucleotide-gated (CNG) channel subunits account for about 80% of all cases of achromatopsia and are associated with progressive cone dystrophies. Cone photoreceptors degenerate over time in patients and in mouse models of CNG channel deficiency. Over the last several years, my laboratory has been investigating the cellular mechanisms of cone degeneration using mouse models with CNG channel deficiency. Upon binding of cyclic guanosine monophosphate (cGMP) under dark conditions, CNG channels open and permit the influx of the calcium and sodium ions necessary to maintain the ...

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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

Get the list of all vendors of CNG kit for Audi A3 near you . Find all the CNG kit for Audi A3 Dealers, importors, distributors and retailers all over at Automoartz, CNG kit for Audi A3 store near you

Hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are responsible for the functional hyperpolarization-activated current (I(h)) in dorsal root ganglion (DRG) neurons. We studied HCN1-4 channel mRNA and protein expression and correlated these findings with I(h) functional properties in rat DRG neurons of different size. Quantitative RT-PCR (TaqMan) analysis demonstrated that HCN2 and HCN1 mRNAs were more abundantly expressed in large diameter (55-80 microm) neurons, while HCN3 mRNA was preferentially expressed in small diameter (20-30 microm) neurons. HCN4 mRNA expression was very low in neurons of all sizes. At the protein level, subunit-selective polyclonal antibodies and immunofluorescence indicated that HCN1 and HCN3 are present in large diameter neurons and small diameter neurons. Staining in small diameter neurons was in IB4-positive (non-peptidergic) and IB4-negative (peptidergic) cells. HCN2 immunofluorescent staining was heterogeneous and predominantly in large diameter ...

Spinal cord injury (SCI) leads to bereft voluntary control of bladder, but the possible role of spontaneous excited system in bladder of SCI patients is poorly understood. Hyper-polarization-activated cyclic nucleotide-gated (HCN) channels are deemed to regulate the spontaneous contraction of bladder, our study explored the functional role of HCN channels in SCI induced neurogenic bladder. Sixty female Sprague-Dawley rats were randomized into control, sham and SCI groups. Rat models subjected to SCI at S2 levels were successfully established and were assessed using hematoxylin and eosin staining and cystometry. In SCI rats, the mRNA and protein expression levels of HCN channels and the Ih density were significantly reduced, and expression levels of several bladder HCN1 channel regulatory proteins were also significantly changed. The effects of 50 µM forskolin and 50 µM 8-bromoadenosine 3,5-cyclic monophosphate on [Ca2+]i of isolated bladder interstitial cells of Cajal-like cells were ...

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.

The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinsons disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive β oscillations, and alleviation of motor deficits in ...

The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinsons disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive β oscillations, and alleviation of motor deficits in ...

Moroni, A., Gorza, L., Beltrame, M., Gravante, B., Vaccari, T., Bianchi, M.E., Altomare, C., Longhi, R., Heurteaux, C., Vitadello, M., Malgaroli, A. and DiFrancesco, D. (2001) Hyperpolarization-activated cyclic nucleotide-gated channel 1 is a molecular determinant of the cardiac pacemaker current If. J. Biol. Chem., 276: 29233-29241 ...

Accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) upregulating its cell-surface expression and current density without affecting its voltage dependence and kinetics.

Hyperpolarization- and Cyclic Nucleotide-gated (HCN) channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. The HCN family consists of four members (HCN1-4). HCN channels represent the molecular correlates of I(h), a hyperpolarization-activated current best known for its role in controlling heart rate and in the regulation of neuronal resting membrane potential and excitability.. HCN channels are unique among vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization. HCN channels are encoded by four genes (HCN1-4) and are widely expressed throughout the heart and the central nervous system.. ...

Hyperpolarization-activated cyclic nucleotide-gated 1on channels (HCN) are gated by voltage, that is, they are able to detect changes in voltage and convert that into work for opening and closing (gating) the channel gate. The focus of this thesis was to investigate the gating mechanisms in HCN channels. Results from these experiments revealed that HCN channels have a voltage sensor (S4) similar to K v channels but have reversed gating. This makes up the first half of the thesis. In addition, the outward currents through HCN channels are susceptible to a voltage-dependent block by intracellular Mg2+. The experiments relating to the Mg2+ block make up the second half of the thesis. HCN channels mediate an inward cation current that contributes to spontaneous rhythmic firing activity in the heart and brain. These channels share homology with depolarization-activated Kv channels, including six transmembrane domains (S 1-S6) and a positively charged S4 segment. The S4 domain has been shown to function as

It is well established that cAMP signaling within neurons plays a major role in the formation of long-term memories. cAMP has three targets, protein kinase A (PKA), hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels, and exchange protein activated by cAMP (Epac). Studies have revealed that both PKA and HCN channels are important for long-term memory formation. However, little is known about the role of Epac in this process. Epac is a cAMP- dependent guanine nucleotide exchange factor for the small G proteins including Rap1.The Epac2 isoform is highly expressed in the forebrain. This dissertation examines the role of Epac in memory formation in several aspects. First, I show that activation of Epac within the hippocampus via intrahippocampal injection of Epac specific agonist 8-pCPT-2-O-Me-cAMP was able to enhance long-term memory formation in a PKA independent fashion. Next, I show that the levels of Rap1 activity, the direct target of Epac, increased during the memory formation.

KCNH channels are voltage-gated potassium channels with important physiological functions. In these channels, a C-terminal cytoplasmic region, known as the cyclic nucleotide binding homology (CNB-homology) domain displays strong sequence similarity to cyclic nucleotide binding (CNB) domains. However, the isolated domain does not bind cyclic nucleotides. Here, we report the X-ray structure of the CNB-homology domain from the mouse EAG1 channel. Through comparison with the recently determined structure of the CNB-homology domain from the zebrafish ELK (eag-like K(+)) channel and the CNB domains from the MlotiK1 and HCN (hyperpolarization-activated cyclic nucleotide-gated) potassium channels, we establish the structural features of CNB-homology domains that explain the low affinity for cyclic nucleotides. Our structure establishes that the self-liganded conformation, where two residues of the C-terminus of the domain are bound in an equivalent position to cyclic nucleotides in CNB domains, is a conserved

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated potassium ion channels. They are, however, activated by hyperpolarizing potentials and are permeable to cations. Four HCN subunits have been cloned, of which HCN1 and HCN2 subunits are p …

2Institute of Neuroscience, National Research Council, Cagliari, Italy. It is widely accepted that ligand-gated and voltage-dependent ion channels are crucial in mediating many of the central pharmacological and behavioral actions of ethanol (EtOH). Recent studies reported that the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels expressed in VTA neurons as well as hippocampal interneurons are modulated by EtOH, suggesting that they may represent an additional sensitive target for this drug. HCN channels are encoded by four HCN genes (HCN1-4), and their activation generates a typical inward current, termed Ih, which plays an important role in controlling neuronal resting membrane potential and firing rate of action potentials, and are heavily implicated in dendritic integration of post-synaptic potentials. Since HCN are highly expressed in CA3 glutamatergic pyramidal neurons, we have investigated the action of EtOH on Ih in these hippocampal cells from ...

Similar experiments were performed with cDNA derived from poly(A)+ RNA of bovine pineal tissue. Two overlapping fragments, harboring either the 5′ or 3′ part of the coding region for rod and cone CNG channels were amplified by two sets of primers similar to those used for amplification of fragments from chick cDNA.. Analysis of genomic structure of chick cone CNG channel. A chick genomic library in λFIXII-vector (Stratagene, La Jolla, Ca) was screened with two cDNA probes (F5′, nucleotides −39 to 926, and F3′, nucleotides 882 to 2391 of pCCG8B; Bönigk et al., 1993). Probe F5′ and F3′ yielded 12 and 7 positive signals, respectively. Two overlapping clones were chosen for further analysis. Clones were digested with SacI, XbaI, EcoRI,BamHI, SalI, and each possible combination of two endonucleases. Fragments were separated by agarose electrophoresis and those containing exon sequences were identified by Southern blotting using probes F5′ and F3′. These fragments were isolated and ...

In situ hybridization studies of mouse brain have revealed distinct but overlapping patterns of expression of HCN1 and HCN2 (Moosmang et al. 1999; Monteggia et al. 2000; Santoro et al. 2000). Single cell PCR studies provide additional strong evidence for coexpression of different HCN isoforms within single neurons (Franz et al. 2000). In particular, both HCN1 and HCN2 are prominently expressed in CA3 and CA1 pyramidal neurons of the hippocampus. Whole-cell patch-clamp recordings demonstrate a prominent Ih current with relatively rapid kinetics in CA1 pyramidal neurons. The presence of multiple HCN isoforms in a given cell raises the question as to whether the Ih current in these cells results from separate populations of homomeric channels or whether the different isoforms coassemble to form heteromultimeric channels.. By coexpressing HCN1 and HCN2 in Xenopus oocytes, we have provided several lines of functional evidence that the two isoforms can indeed coassemble to form functional ...

ID CN15C_MEDTR Reviewed; 703 AA. AC A0A072VMJ3; DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2014, sequence version 1. DT 25-OCT-2017, entry version 20. DE RecName: Full=Protein CNGC15c {ECO:0000303,PubMed:27230377}; DE AltName: Full=Cyclic nucleotide-gated ion channel protein 15 c {ECO:0000303,PubMed:27230377}; GN Name=CNGC15C {ECO:0000303,PubMed:27230377}; GN OrderedLocusNames=MTR_2g094860 {ECO:0000312,EnsemblPlants:KEH39345}; OS Medicago truncatula (Barrel medic) (Medicago tribuloides). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae; OC Pentapetalae; rosids; fabids; Fabales; Fabaceae; Papilionoideae; OC Trifolieae; Medicago. OX NCBI_TaxID=3880 {ECO:0000312,Proteomes:UP000002051}; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Jemalong A17; RX PubMed=22089132; DOI=10.1038/nature10625; RA Young N.D., Debelle F., Oldroyd G.E.D., Geurts R., Cannon S.B., RA Udvardi M.K., ...

ID A0A151R9I9_CAJCA Unreviewed; 418 AA. AC A0A151R9I9; DT 08-JUN-2016, integrated into UniProtKB/TrEMBL. DT 08-JUN-2016, sequence version 1. DT 25-OCT-2017, entry version 7. DE SubName: Full=Putative cyclic nucleotide-gated ion channel 19 {ECO:0000313,EMBL:KYP39025.1}; DE Flags: Fragment; GN ORFNames=KK1_039698 {ECO:0000313,EMBL:KYP39025.1}; OS Cajanus cajan (Pigeon pea) (Cajanus indicus). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae; OC Pentapetalae; rosids; fabids; Fabales; Fabaceae; Papilionoideae; OC Phaseoleae; Cajanus. OX NCBI_TaxID=3821 {ECO:0000313,EMBL:KYP39025.1, ECO:0000313,Proteomes:UP000075243}; RN [1] {ECO:0000313,EMBL:KYP39025.1, ECO:0000313,Proteomes:UP000075243} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Asha {ECO:0000313,Proteomes:UP000075243}; RX PubMed=22057054; DOI=10.1038/nbt.2022; RA Varshney R.K., Chen W., Li Y., Bharti A.K., Saxena R.K., RA Schlueter J.A., Donoghue ...

Lamotrigine (LTG) is generally considered as a voltage-gated sodium (Nav) channel blocker. However, recent studies suggest that LTG can also serve as a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel enhancer and can increase the excitability of GABAergic interneurons (INs). Perisomatic inhibitory INs, predominantly fast-spiking basket cells (BCs), powerfully inhibit granule cells (GCs) in the hippocampal dentate gyrus. Notably, BCs express abundant Nav channels and HCN channels, both of which are able to support sustained action potential generation. Using whole-cell recording in rat hippocampal slices, we investigated the net LTG effect on BC output. We showed that bath application of LTG significantly decreased the amplitude of evoked compound inhibitory postsynaptic currents (IPSCs) in GCs. In contrast, simultaneous paired recordings from BCs to GCs showed that LTG had no effect on both the amplitude and the paired-pulse ratio of the unitary IPSCs, suggesting that LTG did not

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A chronic compression of the DRG (CCD) produces cutaneous hyperalgesia and an enhanced excitability of neuronal somata in the compressed ganglion. The hyperpolarization-activated current (I(h)), present in the somata and axons of DRG neurons, acts to induce a depolarization after a hyperpolarizing event and, if upregulated after CCD, may contribute to enhanced neuronal excitability. Whole-cell patch-clamp recordings were obtained from acutely dissociated, retrogradely labeled, cutaneous, adult rat DRG neurons of medium size. Neurons were dissociated from L4 and L5 control DRGs or DRGs that had each been compressed for 5-7 d by L-shaped rods inserted into the intervertebral foramina. I(h), consisting of a slowly activating inward current during a step hyperpolarization, was recorded from every labeled, medium-sized neuron and was blocked by 1 mm cesium or 15 microm ZD7288. Compared with control, CCD increased the current density and rate of activation significantly without changing its reversal ...

HCN1 antibody [S70-28] (hyperpolarization-activated cyclic nucleotide-gated potassium channel 1) for IHC, IHC-Fr, IP, WB. Anti-HCN1 mAb (GTX41985) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.

The backprojected volume was obtained from image processing of 2D crystal images of the potassium channel MloK1, via a novel software suite implemented in the 2dx and FOCUS software packages (http://focus-em.org). The PCO refined volume was obtained by applying projective constraint optimization to the backprojected volume.

CNGB1 Full-Length MS Protein Standard (NP_001129111), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene.

Neuropathic pain is induced by the injury to nervous systems and characterized by hyperalgesia, allodynia and spontaneous pain. The underlying mechanisms include peripheral and central sensitization resulted from neuronal hyperexcitability. A number of ion channels are considered to contribute to the neuronal hyperexcitability. Here, we particularly concentrate on an interesting ion channel, hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We overview its biophysical properties, physiological functions, followed by focusing on the current progress in the study of its role in the development of neuropathic pain. We attempt to provide a comprehensive review of the potential valuable target, HCN channels, in the treatment of neuropathic pain. ...

Hyperpolarization-activated cAMP-regulated (HCN) channels play important physiological roles in both cardiovascular and central nervous systems. Among the four HCN isoforms, HCN2 and HCN4 show high expression levels in the human heart, with HCN4 being the major cardiac isoform. Previously published crystal structure of mouse HCN2 (mHCN2) C-terminal fragment, including the C-linker and the cyclic-nucleotide binding domain (CNBD), has provided many insights into the cAMP-dependent gating in HCN channels. However, structures of other mammalian HCN channel isoforms have been lacking. Here we used a combination of approaches including structural biology, biochemistry, and electrophysiology, to study the cAMP-dependent gating in HCN4 channels. First we solved the crystal structure of the C-terminal fragment of human HCN4 (hHCN4) channel at 2.4A. Overall we observed a high similarity between mHCN2 and hHCN4 crystal structures. Functional comparison between two isoforms revealed that compared to mHCN2, ...

COMMENT Ih current - hyperpolarization-activated nonspecific Na and K channel - contributes to the resting membrane potential - controls the afterhyperpolarization Reference: 1. Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130, 1996. V1/2 = -84.1 mV k = 10.2 reversal potential = -32.9 +/- 1.1 mV at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms t2 = 1.04+/-0.16 s 2. Maccaferri, G. et al. Properties of the Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993. V1/2 = -97.9 mV k = 13.4 reversal potential = -18.3 mV 3. Pape, H.C. Queer current and pacemaker: The hyperpolarization-activated cation current in neurons, Annu. Rev. Physiol. 58:299-327, 1996. single channel conductance is around ...

COMMENT Ih current - hyperpolarization-activated nonspecific Na and K channel - contributes to the resting membrane potential - controls the afterhyperpolarization Reference: 1. Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current (Ih) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130, 1996. V1/2 = -84.1 mV k = 10.2 reversal potential = -32.9 +/- 1.1 mV at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms t2 = 1.04+/-0.16 s 2. Maccaferri, G. et al. Properties of the Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993. V1/2 = -97.9 mV k = 13.4 reversal potential = -18.3 mV 3. Pape, H.C. Queer current and pacemaker: The hyperpolarization-activated cation current in neurons, Annu. Rev. Physiol. 58:299-327, 1996. single channel conductance is around ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene ...

Function of the hyperpolarization-activated inward rectification in nonmyelinated peripheral rat and human axons.: The function of time-dependent, hyperpolariza

The membrane protein encoded by this gene is a hyperpolarization-activated cation channel that contributes to the native pacemaker currents in heart and neurons. The encoded protein can homodimerize or heterodimerize with other pore-forming subunits to form a potassium channel. This channel may act as a receptor for sour tastes. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments ...

Gabapentin (GBP) is widely used to treat epilepsy and neuropathic pain. There is evidence that GBP can act on HCN channel-mediated Ih in brain slice experiments. However, evidence showing that GBP directly modulates HCN channels is lacking. The effect of GBP was tested using two-electrode voltage clamp recordings from human HCN1, HCN2 and HCN4 channels expressed in Xenopus oocytes. Whole-cell recordings were also made from mouse spinal cord slices targeting either parvalbumin positive (PV+) or calretinin positive (CR+) inhibitory neurons. The effect of GBP on Ih was measured in each inhibitory neuron population. HCN4 expression was assessed in the spinal cord using immunohistochemistry. When applied to HCN4 channels, GBP (100µM) caused a hyperpolarizing shift in the voltage of half activation (V1/2) thereby reducing the currents. GBP had no impact on the V1/2 of HCN1 or HCN2 channels. There was a robust increase in the time to half activation for HCN4 channels with only a small increase noted for HCN1

Like CNG channels, the HCN cation channels are members of the six-transmembrane superfamily (Kaupp and Seifert, 2001; Biel et al., 2002; Robinson and Siegelbaum, 2003). In contrast to most other voltage-gated channels, HCN channels open upon hyperpolarization and close at positive potential. The cyclic nucleotides cAMP and cGMP enhance HCN channel activity by shifting the activation curve of the channels to more positive voltages. The stimulatory effect of cyclic nucleotides does not depend on protein phosphorylation but is caused by direct interaction with the HCN channel protein. The current produced by HCN channels, termed Ih, If, or Iq, is found in a variety of excitable cells, including neurones, cardiac pacemaker cells, and photoreceptors (Pape, 1996; Robinson and Siegelbaum, 2003). The best-understood function of Ih is to control heart rate and rhythm by acting as pacemaker current in the sinoatrial (SA) node (Stieber et al., 2004). Ih is activated during the membrane hyperpolarization ...

Zatebradine Zatebradine(UL-FS49) is a potent HCN channels antagonist, which decreased the heartbeat in a reversible manner; 92% inhibition of the hHCN1-mediated current at 10 uM. ...