Second messenger, cAMP, causes the opening of cation-selective cyclic nucleotide-gated (CNG) channels and depolarization of the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory subunit of this channel which is known to play a central role in the transduction of odorant signals and subsequent adaptation. By accelerating the calcium-mediated negative feedback in olfactory signaling it allows rapid adaptation to odor stimulation and extends its range of odor detection. When heterologously expressed all subunits with exception of CNGA4, CNGB1 and CNGB3 can form functional homomeric channels. In olfactory sensory neurons, CNG channels which are formed by two CNGA2, one CNGA4 subunits and an isoform of CNGB1, are activated by the binding of cAMP, whose levels increase in response to the binding of odorant molecules to their respective receptors. These channels are highly expressed in retinal photoreceptors and olfactory neurons where their role has been extensively studied. CNG channels have also been detected in brain, testis and kidney although their role in these tissues has yet to be unraveled.