دورية أكاديمية
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A hybrid stochastic/deterministic model of single photon response and light adaptation in mouse rods.

التفاصيل البيبلوغرافية
العنوان: A hybrid stochastic/deterministic model of single photon response and light adaptation in mouse rods.
المؤلفون: Beelen CJ; Department of Neuroscience, Division of Biochemistry, University of Oldenburg, 26111 Oldenburg, Germany., Asteriti S; Department of Translational Research, University of Pisa, Pisa 56123, Italy.; Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biological Chemistry, University of Verona, 37134 Verona, Italy., Cangiano L; Department of Translational Research, University of Pisa, Pisa 56123, Italy., Koch KW; Department of Neuroscience, Division of Biochemistry, University of Oldenburg, 26111 Oldenburg, Germany., Dell'Orco D; Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biological Chemistry, University of Verona, 37134 Verona, Italy.
المصدر: Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2021 Jun 23; Vol. 19, pp. 3720-3734. Date of Electronic Publication: 2021 Jun 23 (Print Publication: 2021).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology Country of Publication: Netherlands NLM ID: 101585369 Publication Model: eCollection Cited Medium: Print ISSN: 2001-0370 (Print) Linking ISSN: 20010370 NLM ISO Abbreviation: Comput Struct Biotechnol J Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology
Original Publication: Gothenburg, Sweden : Research Network of Computational and Structural Biotechnology
مستخلص: 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 Ca 2+ -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.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2021 The Author(s).)
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فهرسة مساهمة: Keywords: ADP, adenosine diphosphate; ATP, adenosine-5′-triphosphate; Arr, arrestin; BG, background illumination; CNG, cyclic nucleotide-gated (channel); CSM, completely substituted mutant of rhodopsin; CV, coefficient of variation; DM, deterministic model; Dynamic modeling; E, effector of the phototransduction cascade, activated PDE; FFT, fast Fourier-transform; GC, guanylate cyclase; GCAPs, guanylate cyclase-activating proteins; GDP, guanosine-5′-diphosphate; GPCR, G protein-coupled receptor; GTP, guanosine-5′-triphosphate; Gt, G protein/transducin; Gα, α-subunit of the G protein; Gβγ, β- and γ-subunit of the G protein; HSDM, hybrid stochastic/deterministic model; Light adaptation; MPR, multiple photon response; PDE, phosphodiesterase 6; Ph, photons; Phototransduction; R, rhodopsin; RGS, regulator of G protein signaling; RK, rhodopsin kinase; ROS, rod outer segment; Rec, recoverin; Rn, activated rhodopsin that has been phosphorylated n times; SD, standard deviation; SPR, single photon response; Stochastic simulation; Systems biology; TTP, time to peak; cGMP, cyclic guanosine monophosphate; ΔJ, photocurrent; ΔU, photovoltage
تواريخ الأحداث: Date Created: 20210721 Latest Revision: 20210722
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8258797
DOI: 10.1016/j.csbj.2021.06.033
PMID: 34285774
قاعدة البيانات: MEDLINE
الوصف
تدمد:2001-0370
DOI:10.1016/j.csbj.2021.06.033