Cyclic nucleotide-gated (CNG) channels belong to the superfamily of voltage-gated ion channels. Although permeable to various ions such as the monovalent Na⁺ and K⁺ ions, and the divalent Ca²⁺ ion, they are gated by the intracellular binding of the cyclic nucleotides cAMP and cGMP and not by voltage per se (CNGs bind preferably to cGMP)¹.

Six channels form this subfamily: The A subunit (CNGA1-4) and the B subunit (CNGB1 and CNGB3). Functional entities are formed by the assembly of four subunits. Each subunit consists of six membrane spanning domains, where the fourth transmembrane domain is highly positively charged, a pore domain between transmembrane domains five and six, and intracellular N- and C-termini. The cyclic nucleotide binding domain is located in the C-terminal region and is responsible for the channel gating upon cyclic nucleotide binding¹.

These channels are highly expressed in retinal photoreceptors and olfactory neurons where their role has been extensively studied². CNG channels have also been detected in brain, testis and kidney although their role in these tissues has yet to be unraveled².  

When heterologously expressed all subunits with exception of CNGA4, CNGB1 and CNGB3 can form functional homomeric channels¹. In rod photoreceptors, functional channels are composed of three CNGA1 subunits and one CNGB1 subunit³.

Mutations in either of CNGA1 or CNGB1 genes are responsible for the onset of retinitis pigmentosa, a progressive degeneration of rod and cone receptors which is presented in part by night blindness^3-4. As no knock out CNGA1 model systems exist, a transgenic mice line with lowered CNGA1 protein levels demonstrated symptoms which are reminiscent of retinitis pigmentosa, in agreement with the fact that a lack of CNGA1 is responsible for retinitis pigmentosa⁴.