Cyclic Nucleotide‐gated Ion Channels
Jie Zheng, University of California at Davis, Davis, California, USA
Kimberly Matulef, University of San Diego, San Diego, California, USA
Published online: March 2009
DOI: 10.1002/9780470015902.a0000091.pub2
Abstract
Cyclic nucleotide‐gated (CNG) ion channels are activated by cAMP or cGMP, crucial intracellular messenger molecules that regulate
a wide variety of physiological activities. In photoreceptors and olfactory neurons, CNG channels play an essential role in
transducing sensory stimuli into electrical and chemical responses. CNG channels are also found in other tissues including
brain and sperm, where they may contribute to physiological functions including pacemaking, synaptic transmission and chemosensation.
The exquisite regulation of different CNG channels by divalent cations, calmodulin, phosphorylation and phospholipids allows
these proteins to carry out disparate physiological functions with high precision. Our understanding of the structure of these
channels has been greatly enhanced by the recent determination of the structures of domains of related ion channels. The powerful
combination of electrophysiology, biochemistry, patch‐clamp fluorometry and X‐ray crystallography has begun to unravel the
mystery of how CNG channels are regulated and how the binding of cyclic nucleotides lead to channel opening.
Key concepts
-
Ion channels are membrane proteins that allow ions to diffuse across cellular membranes in a regulated manner.
-
CNG channels are ion channels regulated by the direct binding of cyclic nucleotides.
-
Photoreceptors are retinal cells that contain a high density of ion channels regulated by the binding of cyclic nucleotides.
-
Olfaction is the process of odour sensation, also regulated by the binding of cyclic nucleotides.
-
Permeation describes the ability of ion channels to selectively determine which ions can move through them.
-
Gating is the process by which ion channels open and close to control the flow of ions.
-
Structure/function describes the relationship between the 3D structure of an ion channel and its function.
-
Cyclic nucleotides are small ligands used to control the gating of CNG channels.
Keywords: ion channels; cyclic AMP; cyclic GMP; photoreceptor; olfaction
References
Baylor DA,
Lamb TD and
Yau KW
(1979)
The membrane current of single rod outer segments.
Journal of Physiology
288:
589–611.
Biskup C,
Kusch J,
Schulz E et al.
(2007)
Relating ligand binding to activation gating in CNGA2 channels.
Nature
446(7134):
440–443.
Contreras JE,
Srikumar D and
Holmgren M
(2008)
Gating at the selectivity filter in cyclic nucleotide‐gated channels.
Proceedings of the National Academy of Sciences of the USA
105(9):
3310–3314.
Fesenko EE,
Kolesnikov SS and
Lyubarsky AL
(1985)
Induction by cyclic GMP of cationic conductance in plasma membrane of retinal rod outer segment.
Nature
313(6000):
310–313.
Flynn GE and
Zagotta WN
(2001)
Conformational changes in S6 coupled to the opening of cyclic nucleotide‐gated channels.
Neuron
30(3):
689–698.
Kurahashi T and
Menini A
(1997)
Mechanism of odorant adaptation in the olfactory receptor cell.
Nature
385(6618):
725–729.
Nakamura T and
Gold GH
(1987)
A cyclic nucleotide‐gated conductance in olfactory receptor cilia.
Nature
325(6103):
442–444.
Savchenko A,
Barnes S and
Kramer RH
(1997)
Cyclic‐nucleotide‐gated channels mediate synaptic feedback by nitric oxide.
Nature
390(6661):
694–698.
Shi N,
Ye S,
Alam A,
Chen L and
Jiang Y
(2006)
Atomic structure of a Na+‐ and K+‐conducting channel.
Nature
440(7083):
570–574.
Song Y,
Cygnar KD,
Sagdullaev B et al.
(2008)
Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation.
Neuron
58(3):
374–386.
Zagotta WN,
Olivier NB,
Black KD et al.
(2003)
Structural basis for modulation and agonist specificity of HCN pacemaker channels.
Nature
425(6954):
200–205.
Further Reading
Barnstable CJ,
Wei JY and
Han MH
(2004)
Modulation of synaptic function by cGMP and cGMP‐gated cation channels.
Neurochemistry Internationals
45(6):
875–884.
Biel M and
Michalakis S
(2007)
Function and dysfunction of CNG channels: insights from channelopathies and mouse models.
Molecular Neurobiology
35(3):
266–277.
Bradley J,
Reisert J and
Frings S
(2005)
Regulation of cyclic nucleotide‐gated channels.
Current Opinion in Neurobiology
15(3):
343–349.
Brown RL,
Strassmaier T,
Brady JD and
Karpen JW
(2006)
The pharmacology of cyclic nucleotide‐gated channels: emerging from the darkness.
Current Pharmaceutical Design
12(28):
3597–3613.
Craven KB and
Zagotta WN
(2006)
CNG and HCN channels: two peas, one pod.
Annual Review of Physiology
68:
375–401.
Dowling JE
(1987)
The Retina: An Approachable Part of the Brain.
Cambridge, MA: Belknap Press.
Kaupp UB and
Seifert R
(2002)
Cyclic nucleotide‐gated ion channels.
Physiological Review
82(3):
769–824.
Matulef K and
Zagotta WN
(2003)
Cyclic nucleotide‐gated ion channels.
Annual Review of Cell and Developmental Biology
19:
23–44.
Pifferi S,
Boccaccio A and
Menini A
(2006)
Cyclic nucleotide‐gated ion channels in sensory transduction.
FEBS Letter
22; 580(12):
2853–2859.
Trudeau MC and
Zagotta WN
(2003)
Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide‐gated ion channels.
Journal of Biological Chemistry
278(21):
18705–18708.