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Cyclic nucleotide-regulated channels C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).


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Cyclic nucleotide-gated (CNG) channels are responsible for signalling in the primary sensory cells of the vertebrate visual and olfactory systems.

CNG channels are voltage-independent cation channels formed as tetramers. Each subunit has 6TM, with the pore-forming domain between TM5 and TM6. CNG channels were first found in rod photoreceptors [7,10], where light signals through rhodopsin and transducin to stimulate phosphodiesterase and reduce intracellular cyclic GMP level. This results in a closure of CNG channels and a reduced ‘dark current’. Similar channels were found in the cilia of olfactory neurons [13] and the pineal gland [6]. The cyclic nucleotides bind to a domain in the C terminus of the subunit protein: other channels directly binding cyclic nucleotides include HCN, eag and certain plant potassium channels.

Hyperpolarisation-activated, cyclic nucleotide-gated (HCN)
The hyperpolarisation-activated, cyclic nucleotide-gated (HCN) channels are cation channels that are activated by hyperpolarisation at voltages negative to ~-50 mV. The cyclic nucleotides cyclic AMP and cyclic GMP directly activate the channels and shift the activation curves of HCN channels to more positive voltages, thereby enhancing channel activity. HCN channels underlie pacemaker currents found in many excitable cells including cardiac cells and neurons [5,14]. In native cells, these currents have a variety of names, such as Ih, Iq and If. The four known HCN channels have six transmembrane domains and form tetramers. It is believed that the channels can form heteromers with each other, as has been shown for HCN1 and HCN4 [1]. High resolution structural studies of CNG and HCN channels has provided insight into the the gating processes of these channels [11-12]. A standardised nomenclature for CNG and HCN channels has been proposed by the NC-IUPHAR subcommittee on voltage-gated ion channels [9].

Channels and Subunits

Targets of relevance to immunopharmacology are highlighted in blue

CNGA1 C Show summary » More detailed page

CNGA2 C Show summary » More detailed page

CNGA3 C Show summary » More detailed page

CNGA4 Show summary » More detailed page

CNGB1 Show summary » More detailed page

CNGB3 C Show summary » More detailed page

HCN1 C Show summary » More detailed page

HCN2 C Show summary » More detailed page

HCN3 C Show summary » More detailed page

HCN4 C Show summary » More detailed page


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Further reading

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie A, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. Br J Pharmacol. 176 Issue S1: S142-228.