title: Kinetics of rhodopsin deactivation and its role in regulating recovery and reproducibility of rod photoresponse.
abstract: The single photon response (SPR) in vertebrate phototransduction is regulated by the dynamics of R* during its lifetime, including the random number of phosphorylations, the catalytic activity and the random sojourn time at each phosphorylation level. Because of this randomness the electrical responses are expected to be inherently variable. However the SPR is highly reproducible. The mechanisms that confer to the SPR such a low variability are not completely understood. The kinetics of rhodopsin deactivation is investigated by a Continuous Time Markov Chain (CTMC) based on the biochemistry of rhodopsin activation and deactivation, interfaced with a spatio-temporal model of phototransduction. The model parameters are extracted from the photoresponse data of both wild type and mutant mice, having variable numbers of phosphorylation sites and, with the same set of parameters, the model reproduces both WT and mutant responses. The sources of variability are dissected into its components, by asking whether a random number of turnoff steps, a random sojourn time between steps, or both, give rise to the known variability. The model shows that only the randomness of the sojourn times in each of the phosphorylated states contributes to the Coefficient of Variation (CV) of the response, whereas the randomness of the number of R* turnoff steps has a negligible effect. These results counter the view that the larger the number of decay steps of R*, the more stable the photoresponse is. Our results indicate that R* shutoff is responsible for the variability of the photoresponse, while the diffusion of the second messengers acts as a variability suppressor.
authors.affiliation: Construction Technologies Institute, National Research Council, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caruso
authors.forename: Paolo
authors.initials: P
authors.lastname: Bisegna
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lenoci
authors.forename: Daniele
authors.initials: D
authors.lastname: Andreucci
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Gurevich
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Hamm
authors.forename: Emmanuele
authors.initials: E
authors.lastname: DiBenedetto
mesh_terms: D000818:Animals; D019393:Arrestin / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000378:metabolism; D007700:Kinetics; D008390:Markov Chains; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D010766:Phosphorylation / Q000502:physiology; D017785:Photons; D015203:Reproducibility of Results; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D012243:Rhodopsin / Q000378:metabolism / Q000502:physiology
chemical_list: D019393:Arrestin; D012243:Rhodopsin; D051606:G-Protein-Coupled Receptor Kinase 1