cyclic-gmp and Channelopathies

Recent years have seen an outpouring of atomic or near atomic resolution structures of cyclic nucleotide-gated (CNG) channels, captured in closed, transition, pre-open, partially open, and fully open states. These structures provide unprecedented molecular insights into the activation, assembly, architecture, regulation, and channelopathy of CNG channels, as well as mechanistic explanations for CNG channel biophysical and pharmacological properties. This article summarizes recent advances in CNG channel structural biology, describes key structural features and elements, and illuminates a detailed conformational landscape of activation by cyclic nucleotides. The review also correlates structures with findings and properties delineated in functional studies, including nonselective monovalent cation selectivity, Ca

Topics: Calmodulin; Channelopathies; Cyclic GMP; Cyclic Nucleotide-Gated Cation Channels; Humans; Nucleotides, Cyclic

Cyclic nucleotide-gated (CNG) channels are ion channels which are activated by the binding of cGMP or cAMP. The channels are important cellular switches which transduce changes in intracellular concentrations of cyclic nucleotides into changes of the membrane potential and the Ca2+ concentration. CNG channels play a central role in the signal transduction pathways of vision and olfaction. Structurally, the channels belong to the superfamily of pore-loop cation channels. They share a common domain structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and Eag-like K+ channels. In this chapter, we give an overview on the molecular properties of CNG channels and describe the signal transduction pathways these channels are involved in. We will also summarize recent insights into the physiological and pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient mouse models and human channelopathies.

Topics: Animals; Channelopathies; Cyclic AMP; Cyclic GMP; Cyclic Nucleotide-Gated Cation Channels; Humans; Mice; Mice, Knockout; Olfactory Receptor Neurons; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Signal Transduction