title: Spatiotemporal cGMP dynamics in living mouse rods.
abstract: Signaling of single photons in rod photoreceptors decreases the concentration of the second messenger, cyclic GMP (cGMP), causing closure of cGMP-sensitive channels located in the plasma membrane. Whether the spatiotemporal profiles of the fall in cGMP are narrow and deep, or broad and shallow, has important consequences for the amplification and the fidelity of signaling. The factors that determine the cGMP profiles include the diffusion coefficient for cGMP, the spontaneous rate of cGMP hydrolysis, and the rate of cGMP synthesis, which is powerfully regulated by calcium feedback mechanisms. Here, using suction electrodes to record light-dependent changes in cGMP-activated current in living mouse rods lacking calcium feedback, we have determined the rate constant of spontaneous cGMP hydrolysis and the longitudinal cGMP diffusion coefficient. These measurements result in a fully constrained spatiotemporal model of phototransduction, which we used to determine the effect of feedback to cGMP synthesis in spatially constricting the fall of cGMP during the single-photon response of normal rods. We find that the spatiotemporal cGMP profiles during the single-photon response are optimized for maximal amplification and preservation of signal linearity, effectively operating within an axial signaling domain of ~2 μm.
authors: Center for Neuroscience, University of California, Davis, California, USA.
authors: Owen P
authors: OP
authors: Gross
authors: Edward N
authors: EN
authors: Pugh
authors: Marie E
authors: ME
authors: Burns
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D003624:Darkness; D004058:Diffusion; D051604:Guanylate Cyclase-Activating Proteins / Q000378:metabolism; D015640:Ion Channel Gating / Q000528:radiation effects; D007473:Ion Channels / Q000378:metabolism; D007700:Kinetics; D055537:Light Signal Transduction / Q000528:radiation effects; D051379:Mice; D008954:Models, Biological; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D013997:Time Factors
chemical_list: D051604:Guanylate Cyclase-Activating Proteins; D007473:Ion Channels; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP; D002118:Calcium