Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity.

The Journal of Biological Chemistry
Teresa DudaClint L Makino

Abstract

By generating the second messenger cGMP in retinal rods and cones, ROS-GC plays a central role in visual transduction. Guanylate cyclase-activating proteins (GCAPs) link cGMP synthesis to the light-induced fall in [Ca(2+)]i to help set absolute sensitivity and assure prompt recovery of the response to light. The present report discloses a surprising feature of this system: ROS-GC is a sensor of bicarbonate. Recombinant ROS-GCs synthesized cGMP from GTP at faster rates in the presence of bicarbonate with an ED50 of 27 mM for ROS-GC1 and 39 mM for ROS-GC2. The effect required neither Ca(2+) nor use of the GCAPs domains; however, stimulation of ROS-GC1 was more powerful in the presence of GCAP1 or GCAP2 at low [Ca(2+)]. When applied to retinal photoreceptors, bicarbonate enhanced the circulating current, decreased sensitivity to flashes, and accelerated flash response kinetics. Bicarbonate was effective when applied either to the outer or inner segment of red-sensitive cones. In contrast, bicarbonate exerted an effect when applied to the inner segment of rods but had little efficacy when applied to the outer segment. The findings define a new regulatory mechanism of the ROS-GC system that affects visual transduction and is likely ...Continue Reading

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Citations

Feb 10, 2016·Frontiers in Molecular Neuroscience·Teresa DudaRameshwar K Sharma
Oct 4, 2016·Frontiers in Molecular Neuroscience·Rameshwar K SharmaClint L Makino
Dec 16, 2016·PloS One·Bruno B QueliconiRoberta A Gottlieb
Feb 11, 2018·Molecular and Cellular Biochemistry·Teresa DudaRameshwar K Sharma
Oct 12, 2020·Biochemical Pharmacology·Bianca N QuadeRossana Occhipinti

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