CNG channels are activated by the direct binding of intracellular cyclic nucleotides 18 . They are members of the voltage-gated ion channel superfamily, consisting of four subunits around a centrally located pore. The intracellular carboxy-terminal region of each subunit consists of a C-linker region, a cyclic nucleotide-binding domain (CNBD), and a post-CNBD region (Fig. 1a) . The Xray crystal structure of the carboxy-terminal region of the related hyperpolarization-activated cyclic nucleotide-gated channel reveals a four fold symmetric tetramer with non-interacting CNBDs and extensive intersubunit interactions between C-linker regions 19 .