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Physiol. Rev. 82: 769-824, 2002;
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Physiological Reviews, Vol. 82, No. 3, July 2002, pp. 769-824; 10.1152/physrev.00008.2002.
Copyright ©2002 by the American Physiological Society

Cyclic Nucleotide-Gated Ion Channels

U. Benjamin Kaupp and Reinhard Seifert

Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, Jülich, Germany

Kaupp, U. Benjamin and Reinhard Seifert. Cyclic Nucleotide-Gated Ion Channels. Physiol. Rev. 82: 769-824, 2002.Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila, and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.




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I. I. Senin, D. Hoppner-Heitmann, O. O. Polkovnikova, V. A. Churumova, N. K. Tikhomirova, P. P. Philippov, and K.-W. Koch
Recoverin and Rhodopsin Kinase Activity in Detergent-resistant Membrane Rafts from Rod Outer Segments
J. Biol. Chem., November 19, 2004; 279(47): 48647 - 48653.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
R. Padinjat and S. Andrews
TRP channels at a glance
J. Cell Sci., November 15, 2004; 117(24): 5707 - 5709.
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 Mol. Endocrinol.Home page
J. T. Chun, V. Di Dato, B. D'Andrea, M. Zannini, and R. Di Lauro
The CRE-Like Element Inside the 5'-Upstream Region of the Rat Sodium/Iodide Symporter Gene Interacts with Diverse Classes of b-Zip Molecules that Regulate Transcriptional Activities through Strong Synergy with Pax-8
Mol. Endocrinol., November 1, 2004; 18(11): 2817 - 2829.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
J. Kusch, V. Nache, and K. Benndorf
Effects of permeating ions and cGMP on gating and conductance of rod-type cyclic nucleotide-gated (CNGA1) channels
J. Physiol., November 1, 2004; 560(3): 605 - 616.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
H. Abrahamsen, G. Baillie, J. Ngai, T. Vang, K. Nika, A. Ruppelt, T. Mustelin, M. Zaccolo, M. Houslay, and K. Tasken
TCR- and CD28-Mediated Recruitment of Phosphodiesterase 4 to Lipid Rafts Potentiates TCR Signaling
J. Immunol., October 15, 2004; 173(8): 4847 - 4858.
[Abstract] [Full Text] [PDF]

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 Sci SignalHome page
F. H. Yu and W. A. Catterall
The VGL-Chanome: A Protein Superfamily Specialized for Electrical Signaling and Ionic Homeostasis
Sci. Signal., October 5, 2004; 2004(253): re15 - re15.
[Abstract] [Full Text] [PDF]

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 JGPHome page
M. C. Trudeau and W. N. Zagotta
Dynamics of Ca2+-Calmodulin-dependent Inhibition of Rod Cyclic Nucleotide-gated Channels Measured by Patch-clamp Fluorometry
J. Gen. Physiol., August 30, 2004; 124(3): 211 - 223.
[Abstract] [Full Text] [PDF]

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 JGPHome page
J. W. Karpen
Ion Channel Structure and the Promise of Bacteria: Cyclic Nucleotide-Gated Channels in the Queue
J. Gen. Physiol., August 30, 2004; 124(3): 199 - 201.
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 JGPHome page
C. M. Nimigean, T. Shane, and C. Miller
A Cyclic Nucleotide Modulated Prokaryotic K+ Channel
J. Gen. Physiol., August 30, 2004; 124(3): 203 - 210.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
F. Lemtiri-Chlieh and G. A. Berkowitz
Cyclic Adenosine Monophosphate Regulates Calcium Channels in the Plasma Membrane of Arabidopsis Leaf Guard and Mesophyll Cells
J. Biol. Chem., August 20, 2004; 279(34): 35306 - 35312.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
A. Okada, H. Ueyama, F. Toyoda, S. Oda, W.-G. Ding, S. Tanabe, S. Yamade, H. Matsuura, I. Ohkubo, and K. Kani
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., July 1, 2004; 45(7): 2324 - 2332.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
E. Mo, H. Amin, I. H. Bianco, and J. Garthwaite
Kinetics of a Cellular Nitric Oxide/cGMP/Phosphodiesterase-5 Pathway
J. Biol. Chem., June 18, 2004; 279(25): 26149 - 26158.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
M. L. Woodruff, J. Lem, and G. L. Fain
Early receptor current of wild-type and transducin knockout mice: photosensitivity and light-induced Ca2+ release
J. Physiol., June 15, 2004; 557(3): 821 - 828.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
E. Claes, M. Seeliger, S. Michalakis, M. Biel, P. Humphries, and S. Haverkamp
Morphological Characterization of the Retina of the CNGA3-/-Rho-/- Mutant Mouse Lacking Functional Cones and Rods
Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 2039 - 2048.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. P. Faillace, R. O. Bernabeu, and J. I. Korenbrot
Cellular Processing of Cone Photoreceptor Cyclic GMP-gated Ion Channels: A ROLE FOR THE S4 STRUCTURAL MOTIF
J. Biol. Chem., May 21, 2004; 279(21): 22643 - 22653.
[Abstract] [Full Text] [PDF]

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 JGPHome page
S. L. McCabe, D. M. Pelosi, M. Tetreault, A. Miri, W. Nguitragool, P. Kovithvathanaphong, R. Mahajan, and A. L. Zimmerman
All-trans-retinal Is a Closed-state Inhibitor of Rod Cyclic Nucleotide-gated Ion Channels
J. Gen. Physiol., April 26, 2004; 123(5): 521 - 531.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. P. Tsunoda, B. Wiesner, D. Lorenz, W. Rosenthal, and P. Pohl
Aquaporin-1, Nothing but a Water Channel
J. Biol. Chem., March 19, 2004; 279(12): 11364 - 11367.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
J. D. Brady, T. C. Rich, X. Le, K. Stafford, C. J. Fowler, L. Lynch, J. W. Karpen, R. L. Brown, and J. R. Martens
Functional Role of Lipid Raft Microdomains in Cyclic Nucleotide-Gated Channel Activation
Mol. Pharmacol., March 1, 2004; 65(3): 503 - 511.
[Abstract] [Full Text] [PDF]

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L. Baumann, A. Gerstner, X. Zong, M. Biel, and C. Wahl-Schott
Functional Characterization of the L-type Ca2+ Channel Cav1.4{alpha}1 from Mouse Retina
Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 708 - 713.
[Abstract] [Full Text] [PDF]

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 J Exp BotHome page
I. Cherel
Regulation of K+ channel activities in plants: from physiological to molecular aspects
J. Exp. Bot., February 1, 2004; 55(396): 337 - 351.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
D. Trankner, H. Jagle, S. Kohl, E. Apfelstedt-Sylla, L. T. Sharpe, U. B. Kaupp, E. Zrenner, R. Seifert, and B. Wissinger
Molecular Basis of an Inherited Form of Incomplete Achromatopsia
J. Neurosci., January 7, 2004; 24(1): 138 - 147.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
D.-P. Li, S.-R. Chen, T. F. Finnegan, and H.-L. Pan
Signalling pathway of nitric oxide in synaptic GABA release in the rat paraventricular nucleus
J. Physiol., January 1, 2004; 554(1): 100 - 110.
[Abstract] [Full Text] [PDF]

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 JGPHome page
T. I. Rebrik and J. I. Korenbrot
In Intact Mammalian Photoreceptors, Ca2+-dependent Modulation of cGMP-gated Ion Channels Is Detectable in Cones but Not in Rods
J. Gen. Physiol., December 29, 2003; 123(1): 63 - 76.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. M. Dibb, T. Rose, S. Y. Makary, T. W. Claydon, D. Enkvetchakul, R. Leach, C. G. Nichols, and M. R. Boyett
Molecular Basis of Ion Selectivity, Block, and Rectification of the Inward Rectifier Kir3.1/Kir3.4 K+ Channel
J. Biol. Chem., December 5, 2003; 278(49): 49537 - 49548.
[Abstract] [Full Text] [PDF]

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 JGPHome page
R. L. Brown, L. L. Lynch, T. L. Haley, and R. Arsanjani
Pseudechetoxin Binds to the Pore Turret of Cyclic Nucleotide-gated Ion Channels
J. Gen. Physiol., November 24, 2003; 122(6): 749 - 760.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
B. Much, C. Wahl-Schott, X. Zong, A. Schneider, L. Baumann, S. Moosmang, A. Ludwig, and M. Biel
Role of Subunit Heteromerization and N-Linked Glycosylation in the Formation of Functional Hyperpolarization-activated Cyclic Nucleotide-gated Channels
J. Biol. Chem., October 31, 2003; 278(44): 43781 - 43786.
[Abstract] [Full Text] [PDF]


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