Cyclic nucleotides are important second messengers in many cellular functions such as visual transduction, and relaxation of smooth muscle cells. Cyclic nucleotides exert their cellular functions through three major classes of cellular receptors, one of them is the cyclic nucleotide-gated (CNG) channels.¹ The CNG channels are non-selective cation channels facilitating the influx of Na⁺ and Ca²⁺ ions, following activation by intracellular cyclic nucleotides.² In vertebrates, six members of the CNG channel family were identified and grouped according to sequence homology into two subtypes, CNGA and CNGB. To date, four types of the a subunits (CNGA1-4) and two b subunits (CNGB1, CNGB3) have been characterized.³ 

Native CNG channels are composed of a and b subunits in a tetrameric configuration. Each subunit contains 6 TM domains and intracellular cAMP or cGMP binding domains, but are also modulated by other factors including phosphorylation and calmodulin.⁴ In a heterologous expression system, only the a subunits are capable of forming functional homomeric channels. 

CNG ion channels are essential in visual and olfactory signal transduction.

CNG channels were originally detected in rod and cone photoreceptors and olfactory receptor cells, where they mediate the transduction of external sensory stimuli into neuronal activity.⁵

CNGA2 is predominantly expressed in olfactory neurons (the olfactory type receptor). However, electrophysiological and molecular data indicate that CNGA1, and especially CNGA2, are widely distributed and functionally active in many regions of the brain, including the hippocampus, cerebral cortex, cerebellum, and brainstem.⁶