This a model from the article: Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic reticulum Ca2+ handling and interval-force relations: a modelling study. Iribe G, Kohl P, Noble D. Philos Transact A Math Phys Eng Sci 2006 May 15;364(1842):1107-33 16608699 , Abstract: We hypothesize that slow inactivation of Ca2+/calmodulin-dependent kinase II (CaMKII) and its modulatory effect on sarcoplasmic reticulum (SR) Ca2+ handling are important for various interval-force (I-F) relations, in particular for the beat interval dependency in transient alternans during the decay of post-extrasystolic potentiation. We have developed a mathematical model of a single cardiomyocyte to integrate various I-F relations, including alternans, by incorporating a conceptual CaMKII kinetics model into the SR Ca2+ handling model. Our model integrates I-F relations, such as the beat interval-dependent twitch force duration, restitution and potentiation, positive staircase phenomenon and alternans. We found that CaMKII affects more or less all I-F relations, and it is a key factor for integration of the various I-F relations in our model. Alternans arises, in the model, out of a steep relation between SR Ca2+ load and release, owing to SR load-dependent changes in the releasability of Ca2+ via the ryanodine receptor. Beat interval-dependent CaMKII activity, owing to its kinetic properties and amplifying effect on SR Ca2+ load dependency of Ca2+ release, replicated the beat interval dependency of alternans, as observed experimentally. Additionally, our model enabled reproduction of the effects of various interventions on alternans, such as the slowing or accelerating of Ca2+ release and/or uptake. We conclude that a slow time-dependent factor, represented in the model by CaMKII, is important for the integration of I-F relations, including alternans, and that our model offers a useful tool for further analysis of the roles of integrative Ca2+ handling in myocardial I-F relations. This model was taken from the CellML repository and automatically converted to SBML. The original model was: Iribe G, Kohl P, Noble D. (2006) - version=1.0 The original CellML model was created by: Penny Noble penny.noble@dpag.ox.ac.uk The University of Oxford 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. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. . 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.
Department of Physiology, Anatomy & Genetics, University of Oxford