Abstract
Cyclic nucleotide-gated (CNG) channels are ion channels which are activated by the binding of cGMP or cAMP. The channels are important cellular switches which transduce changes in intracellular concentrations of cyclic nucleotides into changes of the membrane potential and the Ca2+ concentration. CNG channels play a central role in the signal transduction pathways of vision and olfaction. Structurally, the channels belong to the superfamily of pore-loop cation channels. They share a common domain structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and Eag-like K+ channels. In this chapter, we give an overview on the molecular properties of CNG channels and describe the signal transduction pathways these channels are involved in. We will also summarize recent insights into the physiological and pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient mouse models and human channelopathies.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ahnelt PK, Kolb H (2000) The mammalian photoreceptor mosaic-adaptive design. Prog Retin Eye Res 19:711–777
Aligianis IA, Forshew T, Johnson S, Michaelides M, Johnson CA, Trembath RC, Hunt DM, Moore AT, Maher ER (2002) Mapping of a novel locus for achromatopsia (ACHM4) to 1p and identification of a germline mutation in the alpha subunit of cone transducin (GNAT2). J Med Genet 39:656–660
Altenhofen W, Ludwig J, Eismann E, Kraus W, Bonigk W, Kaupp UB (1991) Control of ligand specificity in cyclic nucleotide-gated channels from rod photoreceptors and olfactory epithelium. Proc Natl Acad Sci USA 88:9868–9872
Ardell MD, Bedsole DL, Schoborg RV, Pittler SJ (2000) Genomic organization of the human rod photoreceptor cGMP-gated cation channel beta-subunit gene. Gene 245:311–318
Bakalyar HA, Reed RR (1990) Identification of a specialized adenylyl cyclase that may mediate odorant detection. Science 250:1403–1406
Baker H, Cummings DM, Munger SD, Margolis JW, Franzen L, Reed RR, Margolis FL (1999) Targeted deletion of a cyclic nucleotide-gated channel subunit (OCNC1): biochemical and morphological consequences in adult mice. J Neurosci 19:9313–9321
Bareil C, Hamel CP, Delague V, Arnaud B, Demaille J, Claustres M (2001) Segregation of a mutation in CNGB1 encoding the beta-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa. Hum Genet 108:328–334
Biel M, Zong X, Ludwig A, Sautter A, Hofmann F (1996) Molecular cloning and expression of the Modulatory subunit of the cyclic nucleotide-gated cation channel. J Biol Chem 271:6349–6355
Biel M, Seeliger M, Pfeifer A, Kohler K, Gerstner A, Ludwig A, Jaissle G, Fauser S, Zrenner E, Hofmann F (1999) Selective loss of cone function in mice lacking the cyclic nucleotide-gated channel CNG3. Proc Natl Acad Sci USA 96:7553–7557
Biskup C, Kusch J, Schulz E, Nache V, Schwede F, Lehmann F, Hagen V, Benndorf K (2007) Relating ligand binding to activation gating in CNGA2 channels. Nature 446:440–443
Boccaccio A, Lagostena L, Hagen V, Menini A (2006) Fast adaptation in mouse olfactory sensory neurons does not require the activity of phosphodiesterase. J Gen Physiol 128:171–184
Boekhoff I, Tareilus E, Strotmann J, Breer H (1990) Rapid activation of alternative second messenger pathways in olfactory cilia from rats by different odorants. Embo J 9:2453–2458
Bönigk W, Bradley J, Muller F, Sesti F, Boekhoff I, Ronnett GV, Kaupp UB, Frings S (1999) The native rat olfactory cyclic nucleotide-gated channel is composed of three distinct subunits. J Neurosci 19:5332–5347
Borisy FF, Ronnett GV, Cunningham AM, Juilfs D, Beavo J, Snyder SH (1992) Calcium/calmodulin-activated phosphodiesterase expressed in olfactory receptor neurons. J Neurosci 12:915–923
Bos JL (2006) Epac proteins: multi-purpose cAMP targets. Trends Biochem Sci 31:680–686
Bradley J, Zhang Y, Bakin R, Lester HA, Ronnett GV, Zinn K (1997) Functional expression of the heteromeric “olfactory” cyclic nucleotide-gated channel in the Hippocampus: a potential effector of synaptic plasticity in brain neurons. J Neurosci 17:1993–2005
Bradley J, Bonigk W, Yau KW, Frings S (2004) Calmodulin permanently associates with rat olfactory CNG channels under native conditions. Nat Neurosci 7:705–710
Bradley J, Reisert J, Frings S (2005) Regulation of cyclic nucleotide-gated channels. Curr Opin Neurobiol 15:343–349
Brady JD, Rich ED, Martens JR, Karpen JW, Varnum MD, Brown RL (2006) Interplay between PIP3 and calmodulin regulation of olfactory cyclic nucleotide-gated channels. Proc Natl Acad Sci USA 103:15635–15640
Bright SR, Brown TE, Varnum MD (2005) Disease-associated mutations in CNGB3 produce gain of function alterations in cone cyclic nucleotide-gated channels. Mol Vis 11:1141–1150
Brüggemann A, Pardo LA, Stuhmer W, Pongs O (1993) Ether-a-go-go encodes a voltage-gated channel permeable to K+ and Ca2+ and modulated by cAMP. Nature 365:445–448
Brunet LJ, Gold GH, Ngai J (1996) General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17:681–693
Buck L, Axel R (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65:175–187
Burns ME, Baylor DA (2001) Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annu Rev Neurosci 24:779–805
Cervetto L, Lagnado L, Perry RJ, Robinson DW, McNaughton PA (1989) Extrusion of calcium from rod outer segments is driven by both sodium and potassium gradients. Nature 337: 740–743
Chen TY, Peng YW, Dhallan RS, Ahamed B, Reed RR, Yau KW (1993) A new subunit of the cyclic nucleotide-gated cation channel in retinal rods. Nature 362: 764–767
Chen TY, Takeuchi H, Kurahashi T (2006) Odorant inhibition of the olfactory cyclic nucleotide-gated channel with a native molecular assembly. J Gen Physiol 128:365–371
Claes E, Seeliger M, Michalakis S, Biel M, Humphries P, Haverkamp S (2004) Morphological characterization of the retina of the CNGA3(−/−)Rho(−/−) mutant mouse lacking functional cones and rods. Invest Ophthalmol Vis Sci 45:2039–2048
Clayton GM, Silverman WR, Heginbotham L, Morais-Cabral JH (2004) Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel. Cell 119: 615–627
Coleman JE, Zhang Y, Brown GA, Semple-Rowland SL (2004) Cone cell survival and downreg-ulation of GCAP1 protein in the retinas of GC1 knockout mice. Invest Ophthalmol Vis Sci 45:3397–3403
Craven KB, Zagotta WN (2006) CNG AND HCN CHANNELS: Two Peas, One Pod. Annu Rev Physiol 68:375–401
Cui J, Kagan A, Qin D, Mathew J, Melman YF, McDonald TV (2001) Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2. J Biol Chem 276:17244–17251
Delay R, Restrepo D (2004) Odorant responses of dual polarity are mediated by cAMP in mouse olfactory sensory neurons. J Neurophysiol 92:1312–1319
Dryja TP, Finn JT, Peng YW, McGee TL, Berson EL, Yau KW (1995) Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa. Proc Natl Acad Sci USA 92:10177–10181
Dzeja C, Hagen V, Kaupp UB, Frings S (1999) Ca2+ permeation in cyclic nucleotide-gated channels. Embo J 18:131–144
Eksandh L, Kohl S, Wissinger B (2002) Clinical features of achromatopsia in Swedish patients with defined genotypes. Ophthalmic Genet 23:109–120
Fain GL (2006) Why photoreceptors die (and why they don't). Bioessays 28:344–354
Fain GL, Lisman JE (1999) Light, Ca2+, and photoreceptor death: new evidence for the equivalent-light hypothesis from arrestin knockout mice. Invest Ophthalmol Vis Sci 40: 2770–2772
Fain GL, Matthews HR, Cornwall MC, Koutalos Y (2001) Adaptation in vertebrate photoreceptors. Physiol Rev 81:117–151
Firestein S (2001) How the olfactory system makes sense of scents. Nature 413:211–218
Flynn GE, Black KD, Islas LD, Sankaran B, Zagotta WN (2007) Structure and rearrangements in the carboxy-terminal region of SpIH channels. Structure 15:671–682
Frings S, Seifert R, Godde M, Kaupp UB (1995) Profoundly different calcium permeation and blockage determine the specific function of distinct cyclic nucleotide-gated channels. Neuron 15:169–179
Fu Y, Yau KW (2007) Phototransduction in mouse rods and cones. Pflugers Arch 454:805–819
Fulle HJ, Vassar R, Foster DC, Yang RB, Axel R, Garbers DL (1995) A receptor guanylyl cyclase expressed specifically in olfactory sensory neurons. Proc Natl Acad Sci USA 92:3571–3575
Galindo BE, de la Vega-Beltran JL, Labarca P, Vacquier VD, Darszon A (2007) SptetraKCNG: a novel cyclic nucleotide gated K(+) channel. Biochem Biophys Res Commun 354:668–675
Galindo BE, Neill AT, Vacquier VD (2005) A new hyperpolarization-activated, cyclic nucleotide-gated channel from sea urchin sperm flagella. Biochem Biophys Res Commun 334:96–101
Gauss R, Seifert R, Kaupp UB (1998) Molecular identification of a hyperpolarization-activated channel in sea urchin sperm. Nature 393:583–587
Giorgetti A, Nair AV, Codega P, Torre V, Carloni P (2005) Structural basis of gating of CNG channels. FEBS Lett 579:1968–1972
Gisselmann G, Gamerschlag B, Sonnenfeld R, Marx T, Neuhaus EM, Wetzel CH, Hatt H (2005) Variants of the Drosophila melanogaster Ih-channel are generated by different splicing. Insect Biochem Mol Biol 35:505–514
Gordon SE, Zagotta WN (1995) Localization of regions affecting an allosteric transition in cyclic nucleotide-activated channels. Neuron 14:857–864
Goto-Omoto S, Hayashi T, Gekka T, Kubo A, Takeuchi T, Kitahara K (2006) Compound heterozygous CNGA3 mutations (R436W, L633P) in a Japanese patient with congenital achromatopsia. Vis Neurosci 23:395–402
Haverkamp S, Michalakis S, Claes E, Seeliger MW, Humphries P, Biel M, Feigenspan A (2006) Synaptic plasticity in CNGA3(−/−) mice: cone bipolar cells react on the missing cone input and form ectopic synapses with rods. J Neurosci 26:5248–5255
Higgins MK, Weitz D, Warne T, Schertler GF, Kaupp UB (2002) Molecular architecture of a retinal cGMP-gated channel: the arrangement of the cytoplasmic domains. Embo J 21:2087–2094
Hodgkin AL, McNaughton PA, Nunn BJ (1985) The ionic selectivity and calcium dependence of the light-sensitive pathway in toad rods. J Physiol 358:447–468
Hofmann F, Biel M, Kaupp UB (2005) International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. Pharmacol Rev 57:455–462
Hoshi T (1995) Regulation of voltage dependence of the KAT1 channel by intracellular factors. J Gen Physiol 105:309–328
Hu J, Zhong C, Ding C, Chi Q, Walz A, Mombaerts P, Matsunami H, Luo M (2007) Detection of near-atmospheric concentrations of CO2 by an olfactory subsystem in the mouse. Science 317:953–957
Hüttl S, Michalakis S, Seeliger M, Luo D-G, Acar N, Geiger H, Hudl K, Mader R, Haverkamp S, Moser M, Pfeifer A, Gerstner A, Yau K-W, Biel M (2005) Impaired channel targeting and retinal degeneration in mice lacking the cyclic nucleotide-gated channel subunit CNGB1. J Neu-rosci 25:130–138
Ingram SL, Williams JT (1996) Modulation of the hyperpolarization-activated current (Ih) by cyclic nucleotides in guinea-pig primary afferent neurons. J Physiol 492 (Pt 1):97–106
Jenkins PM, Hurd TW, Zhang L, McEwen DP, Brown RL, Margolis B, Verhey KJ, Martens JR (2006) Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17. Curr Biol 16:1211
Jiang Y, Lee A, Chen J, Cadene M, Chait BT, MacKinnon R (2002) Crystal structure and mechanism of a calcium-gated potassium channel. Nature 417:515–522
Johnson S, Michaelides M, Aligianis IA, Ainsworth JR, Mollon JD, Maher ER, Moore AT, Hunt DM (2004) Achromatopsia caused by novel mutations in both CNGA3 and CNGB3. J Med Genet 41:e20
Juilfs DM, Fulle HJ, Zhao AZ, Houslay MD, Garbers DL, Beavo JA (1997) A subset of olfactory neurons that selectively express cGMP-stimulated phosphodiesterase (PDE2) and guany-lyl cyclase-D define a unique olfactory signal transduction pathway. Proc Natl Acad Sci USA 94:3388–3395
Kalloniatis M, Fletcher EL (2004) Retinitis pigmentosa: understanding the clinical presentation, mechanisms and treatment options. Clin Exp Optom 87:65–80
Kaneko H, Putzier I, Frings S, Kaupp UB, Gensch T (2004) Chloride accumulation in mammalian olfactory sensory neurons. J Neurosci 24:7931–7938
Kaneko H, Mohrlen F, Frings S (2006) Calmodulin contributes to gating control in olfactory calcium-activated chloride channels. J Gen Physiol 127:737–748
Kang K, Bauer PJ, Kinjo TG, Szerencsei RT, Bonigk W, Winkfein RJ, Schnetkamp PP (2003) Assembly of retinal rod or cone Na(+)/Ca(2+) − K(+) exchanger oligomers with cGMP-gated channel subunits as probed with heterologously expressed cDNAs. Biochemistry 42: 4593–4600
Kaupp UB, Niidome T, Tanabe T, Terada S, Bonigk W, Stuhmer W, Cook NJ, Kangawa K, Matsuo H, Hirose T, Miyata T, Numa S (1989) Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342:762–766
Kaupp UB, Seifert R (2002) Cyclic nucleotide-gated ion channels. Physiol Rev 82:769–824
Kelliher KR, Ziesmann J, Munger SD, Reed RR, Zufall F (2003) Importance of the CNGA4 channel gene for odor discrimination and adaptation in behaving mice. Proc Natl Acad Sci USA 100:4299–4304
Kellner U, Wissinger B, Kohl S, Kraus H, Foerster MH (2004) [Molecular genetic findings in patients with congenital cone dysfunction. Mutations in the CNGA3, CNGB3, or GNAT2 genes]. Ophthalmologe 101:830–835
Kennan A, Aherne A, Humphries P (2005) Light in retinitis pigmentosa. Trends Genet 21:103–110
Kingston PA, Zufall F, Barnstable CJ (1996) Rat hippocampal neurons express genes for both rod retinal and olfactory cyclic nucleotide-gated channels: Novel targets for cAMP/cGMP function. Proc Natl Acad Sci USA 93:10440–10445
Kleene SJ, Gesteland RC (1991) Calcium-activated chloride conductance in frog olfactory cilia. J Neurosci 11:3624–3629
Kohl S, Marx T, Giddings I, Jagle H, Jacobson SG, Apfelstedt-Sylla E, Zrenner E, Sharpe LT, Wissinger B (1998) Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel. Nat Genet 19:257–259
Kohl S, Baumann B, Broghammer M, Jagle H, Sieving P, Kellner U, Spegal R, Anastasi M, Zrenner E, Sharpe LT, Wissinger B (2000) Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet 9: 2107–2116
Kohl S, Baumann B, Rosenberg T, Kellner U, Lorenz B, Vadala M, Jacobson SG, Wissinger B (2002) Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Am J Hum Genet 71:422–425
Kohl S, Varsanyi B, Antunes GA, Baumann B, Hoyng CB, Jagle H, Rosenberg T, Kellner U, Lorenz B, Salati R, Jurklies B, Farkas A, Andreasson S, Weleber RG, Jacobson SG, Rudolph G, Castellan C, Dollfus H, Legius E, Anastasi M, Bitoun P, Lev D, Sieving PA, Munier FL, Zrenner E, Sharpe LT, Cremers FP, Wissinger B (2005) CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet 13:302–308
Körschen HG, Illing M, Seifert R, Sesti F, Williams A, Gotzes S, Colville C, Muller F, Dose A, Godde M, et al (1995) A 240 kDa protein represents the complete beta subunit of the cyclic nucleotide-gated channel from rod photoreceptor. Neuron 15:627–636
Kurahashi T, Menini A (1997) Mechanism of odorant adaptation in the olfactory receptor cell. Nature 385:725–729
Kurahashi T, Yau KW (1993) Co-existence of cationic and chloride components in odorant-induced current of vertebrate olfactory receptor cells. Nature 363:71–74
Leconte L, Barnstable CJ (2000) Impairment of rod cGMP-gated channel alpha-subunit expression leads to photoreceptor and bipolar cell degeneration. Invest Ophthalmol Vis Sci 41:917–926
Leinders-Zufall T, Ma M, Zufall F (1999) Impaired odor adaptation in olfactory receptor neurons after inhibition of Ca2+/calmodulin kinase II. J Neurosci 19:RC19
Leinders-Zufall T, Rosenboom H, Barnstable CJ, Shepherd GM, Zufall F (1995) A calcium-permeable cGMP-activated cation conductance in hippocampal neurons. Neuroreport 6: 1761–1765
Leinders-Zufall T, Cockerham RE, Michalakis S, Biel M, Garbers DL, Reed RR, Zufall F, Munger SD (2007) Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium. Proc Natl Acad Sci USA 104:14507–14512
Lin DM, Wang F, Lowe G, Gold GH, Axel R, Ngai J, Brunet L (2000) Formation of precise connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity. Neuron 26:69–80
Lin W, Arellano J, Slotnick B, Restrepo D (2004) Odors detected by mice deficient in cyclic nucleotide-gated channel subunit A2 stimulate the main olfactory system. J Neurosci 24: 3703–3710
Lisman J, Fain G (1995) Support for the equivalent light hypothesis for RP. Nat Med 1:1254–1255
Liu C, Varnum MD (2005) Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit. Am J Physiol Cell Physiol 289:C187–C198
Liu M, Chen TY, Ahamed B, Li J, Yau KW (1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science 266:1348–1354
Long SB, Campbell EB, Mackinnon R (2005) Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309:897–903
Lowe G, Gold GH (1993) Nonlinear amplification by calcium-dependent chloride channels in olfactory receptor cells. Nature 366:283–286
Ma M (2007) Encoding olfactory signals via multiple chemosensory systems. Crit Rev Biochem Mol Biol 42:463–480
Mallouk N, Ildefonse M, Pages F, Ragno M, Bennett N (2002) Basis for intracellular retention of a human mutant of the retinal rod channel alpha subunit. J Membr Biol 185:129–136
Mandiyan VS, Coats JK, Shah NM (2005) Deficits in sexual and aggressive behaviors in Cnga2 mutant mice. Nat Neurosci 8:1660–1662
Matthews HR, Reisert J (2003) Calcium, the two-faced messenger of olfactory transduction and adaptation. Curr Opin Neurobiol 13:469–475
Matulef K, Zagotta WN (2003) Cyclic nucleotide-gated ion channels. Annu Rev Cell Dev Biol 19:23–44
Meyer MR, Angele A, Kremmer E, Kaupp UB, Muller F (2000) A cGMP-signaling pathway in a subset of olfactory sensory neurons. Proc Natl Acad Sci USA 97:10595–10600
Michaelides M, Aligianis IA, Ainsworth JR, Good P, Mollon JD, Maher ER, Moore AT, Hunt DM (2004) Progressive cone dystrophy associated with mutation in CNGB3. Invest Ophthalmol Vis Sci 45:1975–1982
Michalakis S, Geiger H, Haverkamp S, Hofmann F, Gerstner A, Biel M (2005) Impaired opsin targeting and cone photoreceptor migration in the retina of mice lacking the cyclic nucleotide-gated channel CNGA3. Invest Ophthalmol Vis Sci 46:1516–1524
Michalakis S, Reisert J, Geiger H, Wetzel C, Zong X, Bradley J, Spehr M, Hüttl S, Gerstner A, Pfeifer A, Hatt H, Yau KW, Biel M (2006) Loss of CNGB1 protein leads to olfactory dysfunction and subciliary cyclic nucleotide-gated channel trapping. J Biol Chem 281:35156–35166
Mistrik P, Mader R, Michalakis S, Weidinger M, Pfeifer A, Biel M (2005) The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides. J Biol Chem 280:27056–27061
Munger SD, Lane AP, Zhong H, Leinders-Zufall T, Yau KW, Zufall F, Reed RR (2001) Central role of the CNGA4 channel subunit in Ca2+-calmodulin-dependent odor adaptation. Science 294:2172–2175
Nakamura T, Gold GH (1987) A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 325:442–444
Nishiguchi KM, Sandberg MA, Gorji N, Berson EL, Dryja TP (2005) Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum Mutat 25:248–258
Okada A, Ueyama H, Toyoda F, Oda S, Ding WG, Tanabe S, Yamade S, Matsuura H, Ohkubo I, Kani K (2004) Functional role of hCngb3 in regulation of human cone cng channel: effect of rod monochromacy-associated mutations in hCNGB3 on channel function. Invest Ophthalmol Vis Sci 45:2324–2332
Palczewski K, Sokal I, Baehr W (2004) Guanylate cyclase-activating proteins: structure, function, and diversity. Biochem Biophys Res Commun 322:1123–1130
Paoletti P, Young EC, Siegelbaum SA (1999) C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating. J Gen Physiol 113:17–34
Pape HC, Mager R (1992) Nitric oxide controls oscillatory activity in thalamocortical neurons. Neuron 9:441–448
Parent A, Schrader K, Munger SD, Reed RR, Linden DJ, Ronnett GV (1998) Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic nucleotide-gated channel type 1 null mouse. J Neurophysiol 79:3295–3301
Patel KA, Bartoli KM, Fandino RA, Ngatchou AN, Woch G, Carey J, Tanaka JC (2005) Transmem-brane S1 mutations in CNGA3 from achromatopsia 2 patients cause loss of function and impaired cellular trafficking of the cone CNG channel. Invest Ophthalmol Vis Sci 46: 2282–2290
Peng C, Rich ED, Varnum MD (2003) Achromatopsia-associated mutation in the human cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit alters the ligand sensitivity and pore properties of heteromeric channels. J Biol Chem 278:34533–34540
Peng C, Rich ED, Varnum MD (2004) Subunit configuration of heteromeric cone cyclic nucleotide-gated channels. Neuron 42:401–410
Pfeifer A, Ruth P, Dostmann W, Sausbier M, Klatt P, Hofmann F (1999) Structure and function of cGMP-dependent protein kinases. Rev Physiol Biochem Pharmacol 135:105–149
Pierce EA (2001) Pathways to photoreceptor cell death in inherited retinal degenerations. Bioes-says 23:605–618
Pifferi S, Boccaccio A, Menini A (2006a) Cyclic nucleotide-gated ion channels in sensory trans-duction. FEBS Lett 580:2853–2859
Pifferi S, Pascarella G, Boccaccio A, Mazzatenta A, Gustincich S, Menini A, Zucchelli S (2006b) Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduc-tion. Proc Natl Acad Sci USA 103:12929–12934
Poetsch A, Molday LL, Molday RS (2001) The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes. J Biol Chem 276:48009–48016
Pokorny J, Smith VC, Pinckers AJ, Cozijnsen M (1982) Classification of complete and incomplete autosomal recessive achromatopsia. Graefes Arch Clin Exp Ophthalmol 219:121–130
Pugh EN, Jr., Duda T, Sitaramayya A, Sharma RK (1997) Photoreceptor guanylate cyclases: a review. Biosci Rep 17:429–473
Rebrik TI, Korenbrot JI (1998) In intact cone photoreceptors, a Ca2+-dependent, diffusible factor modulates the cGMP-gated ion channels differently than in rods. J Gen Physiol 112:537–548
Reisert J, Lai J, Yau KW, Bradley J (2005) Mechanism of the excitatory Cl- response in mouse olfactory receptor neurons. Neuron 45:553–561
Ressler KJ, Sullivan SL, Buck LB (1994) Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell 79: 1245–1255
Sacks OW (1997) The island of the colorblind, 1st edn. A.A. Knopf, New York
Sautter A, Zong X, Hofmann F, Biel M (1998) An isoform of the rod photoreceptor cyclic nucleotide-gated channel beta subunit expressed in olfactory neurons. Proc Natl Acad Sci USA 95:4696–4701
Schmucker C, Seeliger M, Humphries P, Biel M, Schaeffel F (2005) Grating acuity at different luminances in wild-type mice and in mice lacking rod or cone function. Invest Ophthalmol Vis Sci 46:398–407
Schnetkamp PP (2004) The SLC24 Na+/Ca2+-K+ exchanger family: vision and beyond. Pflugers Arch 447:683–688
Schwarzer A, Schauf H, Bauer PJ (2000) Binding of the cGMP-gated channel to the Na/Ca-K exchanger in rod photoreceptors. J Biol Chem 275:13448–13454
Sharpe LT, Stockman A, Jägle H, Nathans J (1999) Opsin genes, cone photopigments, color vision and colorblindness. Color vision: from genes to perception. Cambridge University Press, Cambridge, UK, pp. 3–52
Shinoda K, Shiotani Y, Osawa Y (1989) “Necklace olfactory glomeruli” form unique components of the rat primary olfactory system. J Comp Neurol 284: 362–373
Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan DR, Aguirre GD, Acland GM, Ostrander EA (2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet 11:1823–1833
Song Y, Cygnar KD, Sagdullaev B, Valley M, Hirsh S, Stephan A, Reisert J, Zhao H (2008) Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation. Neuron 58: 374–86
Spehr M, Wetzel CH, Hatt H, Ache BW (2002) 3-phosphoinositides modulate cyclic nucleotide signaling in olfactory receptor neurons. Neuron 33:731–739
Stieber J, Stockl G, Herrmann S, Hassfurth B, Hofmann F (2005) Functional expression of the human HCN3 channel. J Biol Chem 280:34635–34643
Strünker T, Weyand I, Bonigk W, Van Q, Loogen A, Brown JE, Kashikar N, Hagen V, Krause E, Kaupp UB (2006) A K+-selective cGMP-gated ion channel controls chemosensation of sperm. Nat Cell Biol 8:1149–1154
Sugimoto Y, Yatsunami K, Tsujimoto M, Khorana HG, Ichikawa A (1991) The amino acid sequence of a glutamic acid-rich protein from bovine retina as deduced from the cDNA sequence. Proc Natl Acad Sci USA 88:3116–3119
Sunderman ER, Zagotta WN (1999) Mechanism of allosteric modulation of rod cyclic nucleotide-gated channels. J Gen Physiol 113:601–620
Sundin OH, Yang JM, Li Y, Zhu D, Hurd JN, Mitchell TN, Silva ED, Maumenee IH (2000) Genetic basis of total colourblindness among the Pingelapese islanders. Nat Genet 25:289–293
Szel A, Lukats A, Fekete T, Szepessy Z, Rohlich P (2000) Photoreceptor distribution in the retinas of subprimate mammals. J Opt Soc Am A Opt Image Sci Vis 17:568–579
Taraska JW, Zagotta WN (2007) Structural dynamics in the gating ring of cyclic nucleotide-gated ion channels. Nat Struct Mol Biol 14:854–860
Taylor JP, Hardy J, Fischbeck KH (2002) Toxic proteins in neurodegenerative disease. Science 296:1991–1995
Taylor SS, Kim C, Vigil D, Haste NM, Yang J, Wu J, Anand GS (2005) Dynamics of signaling by PKA. Biochim Biophys Acta 1754:25–37
Tibbs GR, Goulding EH, Siegelbaum SA (1997) Allosteric activation and tuning of ligand efficacy in cyclic-nucleotide-gated channels. Nature 386:612–615
Tränkner D, Jagle H, Kohl S, Apfelstedt-Sylla E, Sharpe LT, Kaupp UB, Zrenner E, Seifert R, Wissinger B (2004) Molecular basis of an inherited form of incomplete achromatopsia. J Neu-rosci 24:138–147
Trudeau MC, Zagotta WN (2002) An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindness. Neuron 34: 197–207
Varnum MD, Black KD, Zagotta WN (1995) Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels. Neuron 15:619–625
Varsanyi B, Wissinger B, Kohl S, Koeppen K, Farkas A (2005) Clinical and genetic features of Hungarian achromatopsia patients. Mol Vis 11:996–1001
Vassar R, Chao SK, Sitcheran R, Nunez JM, Vosshall LB, Axel R (1994) Topographic organization of sensory projections to the olfactory bulb. Cell 79:981–991
Wang F, Nemes A, Mendelsohn M, Axel R (1998) Odorant receptors govern the formation of a precise topographic map. Cell 93:47–60
Weber IT, Gilliland GL, Harman JG, Peterkofsky A (1987) Crystal structure of a cyclic AMP-independent mutant of catabolite gene activator protein. J Biol Chem 262:5630–5636
Wei J, Zhao AZ, Chan GC, Baker LP, Impey S, Beavo JA, Storm DR (1998) Phosphorylation and inhibition of olfactory adenylyl cyclase by CaM kinase II in Neurons: a mechanism for attenuation of olfactory signals. Neuron 21:495–504
Weitz D, Zoche M, Muller F, Beyermann M, Korschen HG, Kaupp UB, Koch KW (1998) Calmod-ulin controls the rod photoreceptor CNG channel through an unconventional binding site in the N-terminus of the beta-subunit. Embo J 17: 2273–2284
Weitz D, Ficek N, Kremmer E, Bauer PJ, Kaupp UB (2002) Subunit stoichiometry of the CNG channel of rod photoreceptors. Neuron 36:881–889
Wenzel A, Grimm C, Samardzija M, Reme CE (2005) Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res 24:275–306
Weyand I, Godde M, Frings S, Weiner J, Muller F, Altenhofen W, Hatt H, Kaupp UB (1994) Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm. Nature 368:859–863
Wiesner B, Weiner J, Middendorff R, Hagen V, Kaupp UB, Weyand I (1998) Cyclic nucleotide-gated channels on the flagellum control Ca2+ entry into sperm. J Cell Biol 142: 473–484
Wissinger B, Gamer D, Jägle H, Giorda R, Marx T, Mayer S, Tippmann S, Broghammer M, Jurklies B, Rosenberg T, Jacobson SG, Sener EC, Tatlipinar S, Hoyng CB, Castellan C, Bitoun P, Andreasson S, Rudolph G, Kellner U, Lorenz B, Wolff G, Verellen-Dumoulin C, Schwartz M, Cremers FP, Apfelstedt-Sylla E, Zrenner E, Salati R, Sharpe LT, Kohl S (2001) CNGA3 mutations in hereditary cone photoreceptor disorders. Am J Hum Genet 69:722–737
Wong ST, Trinh K, Hacker B, Chan GC, Lowe G, Gaggar A, Xia Z, Gold GH, Storm DR (2000) Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27:487–497
Yan C, Zhao AZ, Bentley JK, Loughney K, Ferguson K, Beavo JA (1995) Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons. Proc Natl Acad Sci USA 92:9677–9681
Yang RB, Foster DC, Garbers DL, Fulle HJ (1995) Two membrane forms of guanylyl cyclase found in the eye. Proc Natl Acad Sci USA 92:602–606
Yau KW, Nakatani K (1984) Cation selectivity of light-sensitive conductance in retinal rods. Nature 309:352–354
Yau KW, Nakatani K (1985) Light-induced reduction of cytoplasmic free calcium in retinal rod outer segment. Nature 313:579–582
Yokoyama S (2000) Molecular evolution of vertebrate visual pigments. Prog Retin Eye Res 19:385–419
Yu FH, Yarov-Yarovoy V, Gutman GA, Catterall WA (2005) Overview of molecular relationships in the voltage-gated ion channel superfamily. Pharmacol Rev 57:387–395
Zagotta WN, Olivier NB, Black KD, Young EC, Olson R, Gouaux E (2003) Structural basis for modulation and agonist specificity of HCN pacemaker channels. Nature 425:200–205
Zhao H, Reed RR (2001) X inactivation of the OCNC1 channel gene reveals a role for activity-dependent competition in the olfactory system. Cell 104:651–660
Zheng C, Feinstein P, Bozza T, Rodriguez I, Mombaerts P (2000) Peripheral olfactory projections are differentially affected in mice deficient in a cyclic nucleotide-gated channel subunit. Neuron 26:81–91
Zheng J, Trudeau MC, Zagotta WN (2002) Rod cyclic nucleotide-gated channels have a stoichiom-etry of three CNGA1 subunits and one CNGB1 subunit. Neuron 36:891–896
Zheng J, Zagotta WN (2004) Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels. Neuron 42:411–421
Zhong H, Molday LL, Molday RS, Yau KW (2002) The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420:193–198
Zhong H, Lai J, Yau KW (2003) Selective heteromeric assembly of cyclic nucleotide-gated channels. Proc Natl Acad Sci USA 100:5509–5513
Zhou L, Siegelbaum SA (2007) Gating of HCN channels by cyclic nucleotides: residue contacts that underlie ligand binding, selectivity, and efficacy. Structure 15:655–670
Zong X, Zucker H, Hofmann F, Biel M (1998) Three amino acids in the C-linker are major determinants of gating in cyclic nucleotide-gated channels. Embo J 17:353–362
Zufall F, Munger SD (2001) From odor and pheromone transduction to the organization of the sense of smell. Trends Neurosci 24:191–193
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer
About this chapter
Cite this chapter
Biel, M., Michalakis, S. (2009). Cyclic Nucleotide-Gated Channels. In: Schmidt, H.H.H.W., Hofmann, F., Stasch, JP. (eds) cGMP: Generators, Effectors and Therapeutic Implications. Handbook of Experimental Pharmacology, vol 191. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68964-5_7
Download citation
DOI: https://doi.org/10.1007/978-3-540-68964-5_7
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-68960-7
Online ISBN: 978-3-540-68964-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)