A hybrid stochastic/deterministic model of single photon response and light adaptation in mouse rods
| العنوان: | A hybrid stochastic/deterministic model of single photon response and light adaptation in mouse rods |
|---|---|
| المؤلفون: | Sabrina Asteriti, Karl-Wilhelm Koch, Charlotte Johanna Beelen, Daniele Dell'Orco, Lorenzo Cangiano |
| المصدر: | Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 3720-3734 (2021) Computational and Structural Biotechnology Journal |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | ADP, guanosine-5′-triphosphate, completely substituted mutant of rhodopsin, SPR, Rn, activated rhodopsin that has been phosphorylated n times, Biochemistry, effector of the phototransduction cascade, G protein/transducin, FFT, GPCR, Gt, photons, GC, arrestin, cyclic nucleotide-gated (channel), time to peak, TTP, time to peak, activated PDE, ROS, Stochastic simulation, Rhodopsin kinase, HSDM, hybrid stochastic/deterministic model, RGS, Cascade, Transducin, Gβγ, standard deviation, background illumination, Visual phototransduction, ΔJ, photocurrent, TTP, RGS, regulator of G protein signaling, Biophysics, RK, regulator of G protein signaling, BG, PDE, photocurrent, ΔU, Light adaptation, CSM, Gα, Genetics, G protein-coupled receptor, GPCR, G protein-coupled receptor, β- and γ-subunit of the G protein, SD, Ph, cyclic guanosine monophosphate, rhodopsin kinase, Dynamic modeling, Phototransduction, Systems biology, CSM, completely substituted mutant of rhodopsin, coefficient of variation, multiple photon response, Ph, photons, rhodopsin, cGMP, cyclic guanosine monophosphate, ΔJ, GTP, TP248.13-248.65, Arr, arrestin, Rec, recoverin, Photon, MPR, genetic structures, PDE, phosphodiesterase 6, recoverin, ΔU, photovoltage, Gβγ, β- and γ-subunit of the G protein, phosphodiesterase 6, GDP, Structural Biology, photovoltage, DM, hybrid stochastic/deterministic model, R, rhodopsin, Physics, Rn, biology, adenosine-5′-triphosphate, adenosine diphosphate, GCAPs, GCAPs, guanylate cyclase-activating proteins, HSDM, Computer Science Applications, FFT, fast Fourier-transform, guanylate cyclase, α-subunit of the G protein, Gα, α-subunit of the G protein, BG, background illumination, fast Fourier-transform, Rhodopsin, CNG, cyclic nucleotide-gated (channel), SPR, single photon response, CNG, guanylate cyclase-activating proteins, CV, Arr, E, effector of the phototransduction cascade, activated PDE, GC, guanylate cyclase, Research Article, Biotechnology, Adaptation (eye), guanosine-5′-diphosphate, activated rhodopsin that has been phosphorylated n times, deterministic model, RK, rhodopsin kinase, Patch clamp, ROS, rod outer segment, ComputingMethodologies_COMPUTERGRAPHICS, GTP, guanosine-5′-triphosphate, Gt, G protein/transducin, Rec, CV, coefficient of variation, GDP, guanosine-5′-diphosphate, ATP, adenosine-5′-triphosphate, MPR, multiple photon response, rod outer segment, ADP, adenosine diphosphate, ATP, cGMP, biology.protein, single photon response, sense organs, DM, deterministic model, SD, standard deviation |
| الوصف: | Graphical abstract Highlights • A hybrid stochastic/deterministic model of mouse rod phototransduction is presented. • Rod photocurrent to photovoltage conversion in darkness is accurately characterized. • Photoresponses to dim and bright stimuli and in various mutants are well reproduced. • Recently debated molecular mechanisms of the phototransduction cascade are examined. The phototransduction cascade is paradigmatic for signaling pathways initiated by G protein-coupled receptors and is characterized by a fine regulation of photoreceptor sensitivity and electrical response to a broad range of light stimuli. Here, we present a biochemically comprehensive model of phototransduction in mouse rods based on a hybrid stochastic and deterministic mathematical framework, and a quantitatively accurate description of the rod impedance in the dark. The latter, combined with novel patch clamp recordings from rod outer segments, enables the interconversion of dim flash responses between photovoltage and photocurrent and thus direct comparison with the simulations. The model reproduces the salient features of the experimental photoresponses at very dim and bright stimuli, for both normal photoreceptors and those with genetically modified cascade components. Our modelling approach recapitulates a number of recent findings in vertebrate phototransduction. First, our results are in line with the recently established requirement of dimeric activation of PDE6 by transducin and further show that such conditions can be fulfilled at the expense of a significant excess of G protein activated by rhodopsin. Secondly, simulations suggest a crucial role of the recoverin-mediated Ca2+-feedback on rhodopsin kinase in accelerating the shutoff, when light flashes are delivered in the presence of a light background. Finally, stochastic simulations suggest that transient complexes between dark rhodopsin and transducin formed prior to light stimulation increase the reproducibility of single photon responses. Current limitations of the model are likely associated with the yet unknown mechanisms governing the shutoff of the cascade. |
| اللغة: | English |
| تدمد: | 2001-0370 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8136acd6ea6a307ba719e270e61c52a1 http://www.sciencedirect.com/science/article/pii/S2001037021002713 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8136acd6ea6a307ba719e270e61c52a1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20010370 |
|---|