ABSTRACT
Ion channels that are principally activated by direct binding of intracellular cyclic nucleotides have evolved as cation nonselective transducers for intracellular pathways that regulate synthesis or destruction of cyclic nucleotides. These channels play essential roles in sensory systems, where they interpret the chemical signal produced by external stimulus input – a change in the intracellular concentration of guanosine 3ʹ,5ʹ-cyclic monophosphate (cGMP) or adenosine 3ʹ,5ʹ-cyclic monophosphates (cAMP) – into an electrical response via a change in cation conductance through the channel pore. Cyclic nucleotide-gated (CNG) channels are tetrameric complexes of homologous subunits, with each subunit contributing a cyclic nucleotide-binding domain (CNBD), part of the ion conduction pathway, and the fundamental machinery to covert cGMP or cAMP binding into channel opening. Here, we review their functional and structural properties and their physiological and pathophysiological contributions, with an emphasis on new structural and mechanistic information.
