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Int. J. Mol. Sci. 2018, 19(3), 749; doi:10.3390/ijms19030749

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

Center for Integrated Protein Science Munich (CIPSM), Department of Pharmacy—Center for Drug Research, Ludwig-Maximilians-Universität München, Butenandtstr, 5-13, 81377 Munich, Germany
Author to whom correspondence should be addressed.
Received: 1 February 2018 / Revised: 28 February 2018 / Accepted: 6 March 2018 / Published: 7 March 2018
(This article belongs to the Special Issue cGMP-Signalling in Cells: Molecular and Functional Features)
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The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application. View Full-Text
Keywords: CNG; cyclic nucleotide-gated channel; vision; channelopathies; Ca2+; knockout; photoreceptor; cGMP; gene therapy CNG; cyclic nucleotide-gated channel; vision; channelopathies; Ca2+; knockout; photoreceptor; cGMP; gene therapy

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Michalakis, S.; Becirovic, E.; Biel, M. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy. Int. J. Mol. Sci. 2018, 19, 749.

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