GDP dissociation from Rn_Gt. GDP is taken into account in the rate constant
Rn_G_GTP dissociation to Rn and G_GTP. Here G_GTP is the Gt heterotrimer with bound GTP
Thermal decay of R's catalytic active form MetaII. Rate constant from Xu et al. We assume that the rate constant is independent of the phosphorylation state. See Mitchell DC, Kibelbek J, Litman BJ. (Biochemistry, 1992) for further detail
Rn and RK binding before phospohorylation occurs
Efflux of Ca2+ via the Na+/Ca2+ - K+ exchanger. Note that intracellular Ca2 cannot be lower than Ca2_0
Here PDE has two Ga bound and both its subunits are active
This a model from the article: Network-level analysis of light adaptation in rod cells under normal and altered conditions. Dell'Orco D, Schmidt H, Mariani S, Fanelli F Mol Biosyst 2009 Oct; 5(10):1232-46 19756313 , Abstract: Photoreceptor cells finely adjust their sensitivity and electrical response according to changes in light stimuli as a direct consequence of the feedback and regulation mechanisms in the phototransduction cascade. In this study, we employed a systems biology approach to develop a dynamic model of vertebrate rod phototransduction that accounts for the details of the underlying biochemistry. Following a bottom-up strategy, we first reproduced the results of a robust model developed by Hamer et al. (Vis. Neurosci., 2005, 22(4), 417), and then added a number of additional cascade reactions including: (a) explicit reactions to simulate the interaction between the activated effector and the regulator of G-protein signalling (RGS); (b) a reaction for the reformation of the G-protein from separate subunits; (c) a reaction for rhodopsin (R) reconstitution from the association of the opsin apoprotein with the 11-cis-retinal chromophore; (d) reactions for the slow activation of the cascade by opsin. The extended network structure successfully reproduced a number of experimental conditions that were inaccessible to prior models. With a single set of parameters the model was able to predict qualitative and quantitative features of rod photoresponses to light stimuli ranging over five orders of magnitude, in normal and altered conditions, including genetic manipulations of the cascade components. In particular, the model reproduced the salient dynamic features of the rod from Rpe65(-/-) animals, a well established model for Leber congenital amaurosis and vitamin A deficiency. The results of this study suggest that a systems-level approach can help to unravel the adaptation mechanisms in normal and in disease-associated conditions on a molecular basis. Note: Figure 7 of the reference is reproduced here. Each plot is obtained by increasing flash strength. More details about generating the plots can be obtained from the comments in the curation figure (go to curation tab). This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use . To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
Ca2+ association and dissociation from intracellular buffers, with total concentration eT
Here PDE has two Ga bound but only one active subunit
GTP binding to Ops_G, GDP is taken into account in the rate constant. We assume the same kinetics as in reactions v_r15_*
GDP dissociation from Ops_Gt, GDP is taken into account in the rate constant. Here we assume the same kinetics as in reactions v_r14_*
RK inhibition by Rec_2Ca (Rec_wCa2 is determined using QSSA and not directly)
We assume the reverse reaction to occur with the same rate as v_r13_*
RGS binds to a PDE-Ga complex with both active subunits to form a complex
Gt recycling... heterotrimer reconstitution
Here we assume, according to Felber et al. (1996) that Gt may hydrolize GTP to GDP, and hence inactivate
University of Oldenburg, Institute of Biology and Environmental Sciences
Inactivation of the aPDEa complex by Ga's GTPase capability; here we assume that the same rate constant as above applies
Phosphorylation of Rn to Rn+1. In these reactions ATP (left) and ADP (right) are included in the rate constants
Ops_G_GTP dissociation to Ops and G_GTP, here G_GTP is the Gt heterotrimer with bound GTP. We assume the same kinetics as in reactions v_r16_*
Similarly to Firsov et al. (2006) we consider the rate of Rho regeneration from Ops + 11cis_ret combination as a first order kinetics with the rate constant kRecyc implicitely including 11cis_ret concentration. See paper for details.
One out of two PDE subunits is deactivated and one GTP is hydrolyzed
RGS binds to a PDE-Ga complex with one active subunit to form a complex. Here we assume that the association rate constant is the same as in v_r22
The PDE subunit is deactivated and GTP is hydrolyzed. Here we assume that the deactivation/dissociation rate constant is the same as in v_r23
Influx of extracellular Ca2+ through cGMP-gated cation channels
Inactivation of the PDEa complex by Ga's GTPase capability
GTP binding to Rn_G. GTP is taken into account in the rate constant. Here G is still a heterotrimer and GTP binds to such heterotrimer_R complex
Dissociation of trimeric Gt into alpha and beta-gamma subunits
PDE activation. Here we have the following assumptions on the effector 1) Each PDE subunit may bind Ga_Gtp and become active independently from the other one and with no cooperativity, 2) A PDE hetero-tetramer can hence bind up to 2 different Ga_GTP and thus it works with its in vivo kcat (the reversible reaction is assumed to be possibly present but in this model its rate is set to zero)