Cyclic nucleotide-gated channels: multiple isoforms, multiple roles

Abstract

This chapter presents an overview of cyclic nucleotide-gated (CNG) channels. CNG channels are a family of ligand-gated channels that are activated by the binding of at least two molecules of cAMP or cGMP at intracellular sites on the channel protein. They are nonselective cation channels conducting both mono- and divalent cations and they belong to the superfamily of cation channels with six transmembrane segments. This superfamily includes voltage-gated K + , Na + , and Ca 2+ channels, hyperpolarization-activated cyclic nucleotide gated (HCN) channels, transient receptor potential (TRP) channels, and polycystins. CNG channels were originally identified in vertebrate photoreceptor cells and olfactory receptor neurons (ORNs) where they mediate calcium entry, providing an intracellular calcium signal that is important for both excitation and adaptation. Because of their strong calcium permeability, the activation of CNG channels by the ubiquitous cyclic nucleotide second messengers lead not only to membrane depolarization, but also to a significant calcium influx into the cells. The chapter discusses the structure and nomenclature of CNG channels and their role in the visual transduction cascade. It also elaborates the clinical relevance of CNG channels in channelopathies.