found to be expressed in the brain. Two CNG channel subunits, Tax-2 and Tax-4, have been cloned in C. elegans and are responsible for chemosensation, thermosensation, and normal axon outgrowth of some sensory neurons in C. elegans. The binding event The ligand might be placed at the bottom of the cavity due to interactions with the phosphate binding cassette (PBC). This cavity refers to a region in the CNBD formed by the β roll, a two-looped β helix. Changes induced by ligand binding occur in α helices (αA, αB, and αC and PBC helix). The β roll only undergoes small changes during binding. After the ligand is seated, αB and αC helices arrange themselves so that they form a cap over the cavity. How binding affects the αA helix is still unclear. Cooperative and non-cooperative activation The steep concentration between CNG channels and ligand concentration shows that at least two or three cyclic nucleotides are needed. It is believed that the second ligand is required for the channel to transition from closed to open. When the third and fourth ligands bind, the open state of the channel becomes stabilized. In bacteria, the opening of CNG channels is the result of non-cooperative binding. With differing concentrations of ligands, cooperative binding and non-cooperative binding arise to adapt to these differing environments. At low ligand concentrations, it is rare for a ligand to cooperatively bind, because cooperative binding at low concentrations weakens the binding between channel and ligand, reducing channel sensitivity. Ligand selectivity By measuring the currents activated in excised inside-out membrane patches upon superfusion with varying ligand concentrations, the ligand sensitivity and selectivity of both endogenously and exogenously expressed CNG channels have been studied. All native CNG channels react to both cAMP and cGMP, but smaller concentrations of cGMP than of cAMP are needed to activate and open the channels. CNG channels are sharply selective between cGMP and cAMP in rods and cones, whereas in OSNs, the channels respond equally well to both ligands. CNG channels found in OSNs are much more sensitive to both cGMP and cAMP than photoreceptor CNG channels. Studies of dose response relations showed that channel activation is greatly dependent on cGMP concentration; several cGMP molecules bind to the channel in a cooperative manner. Since each subunit contains a single cNMP-binding site, and homomeric and heteromeric channels most likely form a tetrameric complex, a maximum of four ligand