Structure and function of cyclic nucleotide-gated channels

  • M. Biel
  • X. Zong
  • A. Ludwig
  • A. Sautter
  • F. Hofmann
Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (volume 135)


Cone Photoreceptor Chick Pineal Olfactory Channel Catabolite Gene Activator Protein Photoreceptor Channel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ahmad I, Leinders-Zufall T, Kocsis JD, Shepherd GM, Zufall F, Barnstable CJ (1994). Retinal ganglion cells express a cGMP-gated cation conductance activatable by nitric oxide donors. Neuron 12:155–166Google Scholar
  2. Arancio O, Kandel ER, Hawkins RD (1995) Activity-dependent long-term enhancement of transmitter release by presynaptic 3′,5′-cyclic GMP in cultured hippocampal neurons. Nature 376:74–80Google Scholar
  3. Ardell MD, Aragon I, Oliveira L, Porche GE, Burke E, Pittler SJ (1996) The β subunit of human rod photoreceptor cGMP-gated cation channel is generated from a complex transcription unit. FEBS Lett 389:213–218Google Scholar
  4. Ardell MD, Makhija AK, Olivera L, Miniou P, Viegas-Péquignot E, Pittler SJ (1995) cDNA, gene structure, and chromosomal localisation of human GAR1 (CNCG3L), a homolog of the third subunit of bovine photoreceptor cGMP-gated channel. Genomics 28:32–38Google Scholar
  5. Baumann A, Frings S, Godde M, Seifert R, Kaupp UB (1994) Primary structure and functional expression of a Drosophila cyclic nucleotide-gated channel present in eyes and antennae. EMBO J 13:5040–5050Google Scholar
  6. Baylor D (1996) How photons start vision Proc Natl Acad Sci USA 93:560–565Google Scholar
  7. Beavo JA (1995) Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 75:725–748Google Scholar
  8. Berghard A, Buck LB, Liman ER (1996) Evidence for distinct signaling mechanism in two mammalian olfactory sense organs. Proc Natl Acad Sci USA 93:2365–2369Google Scholar
  9. Biel M, Zong X, Distler M, Bosse E, Klugbauer N, Murakami M, Flockerzi V, Hofmann F (1994) Another member of the cyclic nucleotide-gated channels family expressed in testis, kidney and heart. Proc Natl Acad Sci USA 91:3505–3509Google Scholar
  10. Biel M, Zong X, Hofmann F (1996a) Cyclic nucleotide-gated cation channels: molecular diversity, structure and cellular functions. Trends Cardiovasc Med 6:274–280Google Scholar
  11. Biel M, Zong X, Ludwig A, Sautter A, Hofmann F (1996b) Molecular cloning and expression of a modulatory subunit of the cyclic nucleotide-gated cation channel. J Biol Chem 271:6349–6355Google Scholar
  12. Bönigk W, Altenhofen W, Müller F, Dose A, Illing M, Molday RS, Kaupp UB (1993) Rod and cone photoreceptor cells express distinct genes for cGMP-gated channels. Neuron 10:865–877Google Scholar
  13. Bönigk W, Müller F, Middendorff R, Weyand I, Kaupp UB (1996) Two alternatively spliced forms of the cGMP-gated channel α-subunit from cone photoreceptor are expressed in the chick pineal organ. J Neuroscience 16:7458–7468Google Scholar
  14. Bradley J, Li J, Davidson N, Lester HA, Zinn K (1994) Heteromeric olfactory cyclic nucleotide-gated channels: A new subunit that confers increased sensitivity to cAMP. Proc Natl Acad Sci USA 91:8890–8894Google Scholar
  15. Bradley J, Zhang Y, Bakin R, Lester HA, Ronnett GV, Zinn K (1997) Functional expression of the heteromeric “olfactory” cyclic nucleotide-gated channel in hippocampus: a potential effector of synaptic plasticity in brain neurons. J Neuroscience 17:1993–2005Google Scholar
  16. Breer H, Raming K, Krieger J (1994) Signal recognition and transduction in olfactory neurons. Biochim Biophys Acta 1224:277–287Google Scholar
  17. Broillet MC, Firestein S (1996) Direct activation of the olfactory cyclic nucleotidegated channel through modification of sulfhydryl groups by NO compounds. Neuron 16:377–385Google Scholar
  18. Broillet MC, Firestein S (1997) β subunits of the olfactory cyclic nucelotide-gated channel form a nitric oxide activated Ca2+ channel. Neuron 18:951–958Google Scholar
  19. Brown RL, Gramling R, Bert RJ, Karpen JW (1995) Cyclic GMP contact points within the 63-kDa subunit and a 240-kDa associated protein of retinal rod cGMP-activated channels. Biochemistry 34:8365–8370Google Scholar
  20. Brunet LJ, Gold GH, Ngai J (1996) General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17:681–693Google Scholar
  21. Chen TY, Illing M, Hsu YT, Yau KW, Molday RS (1994) Subunit 2 (or β) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca2+-calmodulin modulation. Proc Natl Acad Sci USA 91:11757–11761Google Scholar
  22. 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 362:764–767Google Scholar
  23. Chen TY, Yau KW (1994) Direct modulation by Ca2+-calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons. Nature 368:545–548Google Scholar
  24. Cobbs WH, Barkdoll AE III, Pugh EN Jr (1985) Cyclic GMP increases photocurrent and light sensitivity of retinal cones. Nature 317:64–66Google Scholar
  25. Coburn CM, Bargmann CI (1996) A putative cyclic nucleotide-gated channel is required for sensory development and function in C. elegans. Neuron 17:695–706Google Scholar
  26. Colamartino G, Menini A, Torre V (1991) Blockage and permeation of divalent cations through the cyclic GMP-activated channel from tiger salamander retinal rods. J Physiol 440:189–206Google Scholar
  27. Colville CA, Molday RS (1996) Primary structure and expression of the human β-subunit and related proteins of the rod photoreceptor cGMP-gated channel. J Biol Chem 271:32968–32974Google Scholar
  28. Cook NJ, Hanke W, Kaupp UB (1987) Identification, purification, and functional reconstitution of the cyclic GMP-dependent channels from rod photoreceptors. Proc Natl Acad Sci USA 84:585–589Google Scholar
  29. Dhallan RS, Yau KW, Schrader KA, Reed RR (1990) Primary structure and functional expression of a cyclic nucleotide-activated channel from olfactory neurons. Nature 347:184–187Google Scholar
  30. Ding C, Potter ED, Qiu W, Coon SL, Levine MA, Guggino SE (1997) Cloning and widespread distribution of the rat rod-type cyclic nucleotide-gated cation channel. Am J Physiol 272:C1335–1344Google Scholar
  31. Distler M, Biel M, Flockerzi V, Hofmann F (1994) Expression of cyclic nucleotidegated cation channels in non-sensory tissues and cells. Neuropharmacology 33:1275–1282Google Scholar
  32. Doyle DA, Cabral JM, Pfuetzner RA, Kuo A, Gulbis J, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77Google Scholar
  33. Dryer S, Henderson D (1991) A cyclic GMP-activated channel in dissociated cells of chick pineal gland. Nature 353:756–758Google Scholar
  34. Eismann E, Müller F, Heinemann SH, Kaupp UB (1994) A single negative charge within the pore region of a cGMP-gated channel controls rectification, Ca2+ blockage, and ion selectivity. Proc Natl Acad Sci USA 91:1109–1113Google Scholar
  35. Fesenko EE, Kolesnikov SS, Lyubarsky AL (1985) Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segments. Nature 313:310–313Google Scholar
  36. Finn JT, Grunwald ME, Yau KW (1996) Cyclic nucleotide-gated ion channels: an extanded family with diverse functions. Annu Rev Physiol 58:395–426Google Scholar
  37. Finn JT, Solessio EC, Yau KW (1997) A cGMP-gated cation channel in depolarizing photoreceptors of the lizard parietal eye. Nature 385:815–819Google Scholar
  38. Firestein S (1992) Electric signals in olfactory transduction. Current Opinion in Neurobiology 2:444–448Google Scholar
  39. Frings S, Lynch JW, Lindemann B (1992) Properties of cyclic nucleotide-gated channels mediating olfactory transduction: Activation, selectivity, and blockage. J Gen Physiol 100:45–67Google Scholar
  40. 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 15:169–179Google Scholar
  41. Garbers DL (1989) Molecular basis of fertilization. Annu Rev Biochem 58:719–742Google Scholar
  42. Goldstein SAN (1996) A structural vignette common to voltage sensors and conduction proes: canaliculi. Neuron 16:717–722Google Scholar
  43. Gordon SE, Downing-Park J, Zimmerman AL (1995) Modulation of the cGMP-gated ion channel in frog rods by calmodulin and an endogenous inhibitory factor. J Physiol 486:533–546Google Scholar
  44. Gordon SE, Oakley JC, Varnum MD, Zagotta WN (1996) Altered ligand specificity by protonation in the ligand binding domain of cyclic nucleotide-gated channels. Biochemistry 35:3994–4001Google Scholar
  45. Gordon SE, Varnum MD, Zagotta WN (1997) Direct interaction between amino-and carboxyl-terminal domains of cyclic nucleotide-gated channels. Neuron 19:431–441Google Scholar
  46. Gordon SE, Zagotta WN (1995a). Subunit interactions in coordination of Ni2+ in cyclic nucleotide-gated channels. Proc Natl Acad Sci USA 92:10222–10226Google Scholar
  47. Gordon SE, Zagotta WN (1995b) Localization of regions affecting an allosteric transition in cyclic nucleotide-activated channels. Neuron 14:857–864Google Scholar
  48. Gordon SE, Zagotta WN (1995c) A histidine residue associated with the gate of the cyclic nucleotide-activated channels in rod photoreceptors. Neuron 14:177–183Google Scholar
  49. Goulding EH, Tibbs GR, Liu D, Siegelbaum SA (1993) Role of H5 domain in determining pore diameter and ion permeation through cyclic nucleotide-gated channels. Nature 364:61–64Google Scholar
  50. Goulding EH, Tibbs GR, Siegelbaum SA (1994) Molecular mechanism of cyclic nucleotide-gated channel activation. Nature 372:369–374Google Scholar
  51. Grunwald ME, Yu WP, Yu HH, Yau KW (1998) Identification of a domain on the β-subunit of the rod cGMP-gated cation channel that mediates inhibition by calcium-calmodulin. J Biol Chem 273:9148–9157Google Scholar
  52. Guy HR, Durell SR, Warmke J, Drysdale R, Ganetzky B (1991) Similarities in amino acid sequences of Drosophila eag and cyclic nucleotide-gated channels. Science 254:730Google Scholar
  53. Hatt H, Ache BW (1994) Cyclic nucleotide-and inositol phosphate-gated ion channels in lobster olfactory neurons. Proc Natl Acad Sci USA 91:6264–6268Google Scholar
  54. Haynes LW (1995a) Permeation of internal and external monovalent cations through the catfish cone photoreceptor cGMP-gated channel. J Gen Physiol 106:485–505Google Scholar
  55. Haynes LW (1995b) Permeation and block by internal and external cations of the catfish cone photoreceptor cGMP-gated channel. J Gen Physiol 106:507–523Google Scholar
  56. Haynes LW, Yau KW (1985) Cyclic GMP-sensitive conductance in outer segment membrane of the catfish cones. Nature 317:61–64Google Scholar
  57. Heginbotham L, Abramson T, MacKinnon R (1992) A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels. Science 258:1152–1155Google Scholar
  58. Henn DK, Baumann A, Kaupp UB (1995) Probing the transmembrane topology of cyclic nucleotide-gated ion channels with a gene fusion approach. Proc Natl Acad Sci USA 92:7425–7429Google Scholar
  59. Hess P, Tsien RW (1984) Mechanism of ion permeation through calcium channels. Nature 309:453–456Google Scholar
  60. Hofmann F, Dostmann W, Keilbach A, Landgraf W, Ruth P (1992) Structure and physiological role of cGMP-dependent protein kinase. Biochem Biophys Acta 1135:51–60Google Scholar
  61. Hofmann F, Ludwig A, Pfeifer A (1994) Cyclic GMP and the control of airways smooth muscle tone. In: Raeburn D, Giembycz MA (eds) Airways smooth muscle: Biochemical control of contraction and relaxation. Birkhäuser Verlag, Basel, pp 253–269Google Scholar
  62. Hoshi T, Zagotta WN, Aldrich RW (1990) Biophysical and molecular mechanism of Shaker potassium channel inactivation. Science 250:533–538Google Scholar
  63. Hsu YT, Molday RS (1993) Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin. Nature 361:76–79Google Scholar
  64. Ikura M, Clore GM, Gronenborn AM, Zhu G, Klee CB, Bax A (1992) Solution structure of a calmodulin-target peptide complex by multidimensional NMR. Science 256:632–638Google Scholar
  65. Jan LY, Jan YN (1992) Structural elements involved in specific K+ channel functions. Annu Rev Physiol 54:537–555Google Scholar
  66. Kaupp UB, Niidome T, Tanabe T, Terada S, Bönigk W, Stühmer 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 342:762–766Google Scholar
  67. 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 93:10440–10445Google Scholar
  68. Komatsu H, Mori I, Rhee JS, Akaike N, Ohshima Y (1996) Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. elegans. Neuron 17:707–718Google Scholar
  69. Körschen HG, Illing M, Seifert R, Sesti F, Williams A, Gotzes S, Colville C, Müller F, Dose A, Godde M, Molday L, Kaupp UB, Molday RS (1995) A 240 kDa protein represents the complete β subunit of the cyclic nucleotide-gated channel from rod photoreceptor. Neuron 15:627–636Google Scholar
  70. Kramer RH, Goulding E, Siegelbaum SA (1994) Potassium channel inactivation peptide blocks cyclic nucleotide-gated channels by binding to the conserved pore domain. Neuron 12:655–662Google Scholar
  71. Kumar VD, Weber IT (1992) Molecular model of the cyclic GMP-binding domain of the cyclic GMP-gated ion channel. Biochemistry 31:4643–4649Google Scholar
  72. Kurahashi T, Menini A (1997) Mechanism of odorant adaptation in the olfactory receptor cell. Nature 385:725–729Google Scholar
  73. Liman ER, Buck LB (1994) A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP. Neuron 13:611–621Google Scholar
  74. Liu DT, Tibbs GR, Siegelbaum SA (1996) Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function. Neuron 16:983–990Google Scholar
  75. Liu M, Chen TY, Ahamed B, Li J, Yau KW (1994) Calcium-calmodulin modulation of the olfactory cyclic nucleotide-gated cation channel. Science 266:1348–1354Google Scholar
  76. MacKinnon R (1995) Pore loops: an emerging theme in ion channel structure. Neuron 14:889–892Google Scholar
  77. McKay DB, Steitz TA (1981) Structure of catabolite gene activator protein at 2.9 A resolution suggests binding to left-handed B-DNA. Nature 290:744–749Google Scholar
  78. Menini A (1990) Currents carried by monovalent cations through cyclic GMP-activated channels in excised patches from salamander rods. J Physiol 424:167–185Google Scholar
  79. Misaka T, Kusakabe Y, Emori Y, Gonoi T, Arai S, Abe K (1997) Taste buds have a cyclic nucleotide-activated channel, CNGgust. J Biol Chem 272:22623–22629Google Scholar
  80. Molday RS, Molday LL, Dose A, Clark-Lewis I, Illing M, Cook NJ, Eismann E, Kaupp UB (1991) The cGMP-gated channel of the rod photoreceptor cell: Characterization and orientation of the amino terminus. J Biol Chem 266:21917–21922Google Scholar
  81. Nakamura T, Gold GH (1987) A cyclic nucleotide-gated conductance in olfactory receptor cilia. Nature 325:442–444Google Scholar
  82. Nawy S, Jahr CE (1991) cGMP-gated conductance in retinal bipolar cells is suppressed by the photoreceptor transmitter. Neuron 7:677–683Google Scholar
  83. Root MJ, MacKinnon R (1993) Identification of an external divalent cation-binding site in the the pore of a cGMP-activated channel. Neuron 11:459–466Google Scholar
  84. Ruiz ML, Karpen JW (1997) Single cyclic nucleotide-gated channels locked in different ligand-bound states. Nature 389:389–392Google Scholar
  85. Sautter A, Biel M, Hofmann F (1997) Molecular cloning of cyclic nucleotide-gated cation channel subunits from rat pineal gland. Mol Brain Res 48:171–175Google Scholar
  86. Sautter A, Zong X, Hofmann F, Biel M (1998). An isoform of the rod photoreceptor cyclic nucleotide-gated channel β subunit expressed in olfactory neurons. Proc Natl Acad USA 95:4696–4701Google Scholar
  87. Savchenko A, Barnes S, Kramer RH (1997) Cyclic-nucleotide-gated channels mediate synaptic feedback by nitric oxide. Nature 390:694–698Google Scholar
  88. Schaad NC, Vanecek J, Rodriguez IR, Klein DC, Holtzclaw L, Russel JT (1995) Vasoactive intestinal peptide elevates pinealocyte intracellular calcium concentrations by enhancing influx: evidence for involvement of a cyclic GMP-dependent mechanism. Mol Pharmacol 47:923–933Google Scholar
  89. Sesti F, Eismann E, Kaupp UB, Nizzari M, Torre V (1995) The multi-ion nature of the cGMP-gated channel from vertebrate rods. J Physiol 487:17–36Google Scholar
  90. Shabb JB, Corbin JD (1992) Cyclic nucleotide-binding domains in proteins having diverse functions. J Biol Chem 267:5723–5726Google Scholar
  91. Shiells RA, Falk G (1990) Glutamate receptors of rod bipolar cells are linked to a cyclic GMP cascade via a G-protein. Proc R Soc Lond 242:91–94Google Scholar
  92. 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 88:3116–3119Google Scholar
  93. Sun ZP, Akabas MH, Goulding EH, Karlin A, Siegelbaum SA (1996) Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating. Neuron 16:141–149Google Scholar
  94. Tang CY, Papazian DM (1997) Transfer of voltage independence from a rat olfactory channel to the Drosophila ether-à-go-go K+-channel. J Gen Physiol 109:301–311Google Scholar
  95. Thompson SH (1997) Cyclic GMP-gated channels in a sympathetic neuron cell line. J Gen Physiol 110:155–164Google Scholar
  96. Tibbs GR, Goulding EH, Siegelbaum SA (1997) Allosteric activation and tuning of ligand efficacy in cyclic nucleotide-gated channels. Nature 86:612–615Google Scholar
  97. Torre V, Straforini M, Sesti F, Lamb TD (1992) Different channel-gating properties of two classes of cyclic GMP-activated channel in vertebrate photoreceptors. Proc R Soc London Ser B 250:209–215Google Scholar
  98. Vaandrager AB, De Jonge HR (1994) Effect of cyclic GMP on intestinal transport. Adv Pharmacol 26:252–282Google Scholar
  99. Varnum MD, Black KD, Zagotta WN (1995) Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels. Neuron 15:619–625Google Scholar
  100. Varnum MD, Zagotta WN (1997) Interdomain interactions underlying activation of cyclic nucleotide-gated channels. Science 278:110–113Google Scholar
  101. Weitz D, Zoche M, Müller F, Beyermann M, Körschen HG, Kaupp UB, Koch KW (1998) Calmodulin controls the rod photoreceptor CNG channel through an unconventional binding site in the N-terminus of the β-subunit. EMBO J 17:2273–2284Google Scholar
  102. Weyand I, Godde M, Frings S, Weiner J, Müller F, Altenhofen W, Hatt H, Kaupp UB (1994) Cloning and functional expression of a cyclic nucleotide-gated channel from mammalian sperm. Nature 368:859–863Google Scholar
  103. Yang J, Ellinor PT, Sather WA, Zhang JF, Tsien RW (1993) Molecular determinants of Ca2+ selectivity and ion permeation of L-type Ca2+ channels. Nature 366:158–161Google Scholar
  104. Yau KW, Nakatani K (1985) Light-suppressible, cyclic GMP-sensitive conductance in the plasma membrane of a truncated rod outer segment. Nature 317:252–255Google Scholar
  105. Zagotta WN, Siegelbaum SA (1996) Structure and function of cyclic nucleotide-gated channels. Annu Rev Neurosci 19:235–263Google Scholar
  106. Zimmerman AL, Baylor DA (1992) Cation interactions within the cyclic GMP-activated channel of retinal rods from the tiger salamander. J Physiol 449:759–783Google Scholar
  107. 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 17:353–362Google Scholar
  108. Zufall F, Firestein S (1993) Divalent cations block the cyclic nucleotide-gated channel of olfactory receptor neurons. J Neurophysiol 69:1758–1768Google Scholar
  109. Zufall F, Firestein S, Shepherd GM (1994) Cyclic nucleotide-gated ion channels and sensory transduction in olfactory receptor neurons. Annu Rev Biophys Biomol Struct 23:577–607Google Scholar
  110. Zufall F, Shepherd GM, Barnstable CJ (1997) Cyclic nucleotide-gated channels as regulator of CNS development and plasticity. Curr Opin Neurobiol 7:404–412Google Scholar

Copyright information

© Springer-Verlag 1999

Authors and Affiliations

  • M. Biel
    • 1
  • X. Zong
    • 1
  • A. Ludwig
    • 1
  • A. Sautter
    • 1
  • F. Hofmann
    • 1
  1. 1.Institut für Pharmakologie und Toxikologie der Technischen Universität MünchenMünchenGermany

Personalised recommendations