Cyclic Nucleotide Gated (CNG) Channels

Cyclic nucleotide gated (CNG) channels are non-selective cation channels facilitating the influx of Na⁺ and Ca²⁺ ions, with their opening dependent on a cyclic nucleotide binding to the channel complex. Therefore, these channels couple electrical and/or Ca²⁺ signals to cyclic nucleotide concentration and are important links in both visual and olfactory signal transduction (for reviews see^1-4). In addition CNG channels are modulated by other factors including phosphorylation and calmodulin⁵. An exogenous modulator, Pseudoechetoxin, a peptide snake toxin, blocked CNG2 expressed in Xenopus oocytes⁶.

CNG channels are constructed of α and β subunits in a likely tetrameric configuration. Both types of subunits contain 6 TM domains and intracellular cAMP or cGMP binding domains. The difference between α and β subunits is that, when expressed in heterologous systems, α subunits form functional ion channels, while β subunits only modulate the characteristics of α subunits.

To date, three types of α subunits (CNG1-3) and three β subunits (CNG4-6) have been characterized: encoding channels found in rod photoreceptors (CNG1⁷, CNG4⁸), olfactory epithelia (CNG2^9-10, CNG4¹¹, CNG5¹²)¹³, and cone photoreceptor (CNG3¹⁴, CNG6¹⁵). Despite the primary detection in these types of cells, CNG1 mRNA is expressed in endothelial and smooth muscle vascular cells¹⁶. CNG2 channels are widely expressed in CNS^17-18, and CNG3 is expressed in testis¹⁹. In accordance with CNG2 distribution, knockout of this gene produced altered hippocampal long term potentiation (LTP) in mice²⁰.

Humans with color blindness were found to carry mutations in one of both subunits of cone photoreceptor CNG channels (see²¹), highlighting both the importance and physiological role of these channels.

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