%0 Journal Article %1 Hinc_2004_3723 %A Hinch, R. %A Greenstein, J. L. %A Tanskanen, A. J. %A Xu, L. %A Winslow, R. L. %D 2004 %J Biophys. J. %K AMP-Dependent Acid Action Adaptor Adrenergic, Algorithms, Amino Animals, Biological, Biophysics, Calcium Calcium, Cardiac, Cardiovascular, Cell Cells, Chains, Channel Channel, Channels, Comparative Complexes, Computer Conduction Contraction, Cyclic Dependent Dogs, Electrophysiology, Expression Extramural, Factors, Gating, Gene Gov't, Guinea Heart Humans, Interaction Ion Ions, Isoproterenol, Kinase, Kinases, L-Type, Long Mapping, Markov Membrane Membrane, Models, Multiprotein Muscle Myocardial Myocardium, Myocytes, N.I.H., Neurons, Non-U.S. P.H.S., Phosphatase, Phosphoprotein Phosphorylation, Pigs, Post-Translational, Potassium Potentials, Processes, Processing, Profiling, Protein Proteins, Proteome, Proteomics, QT Receptor Receptors, Regulation, Relationship, Release Research Ryanodine Ryanodine, Signal Signaling, Simulation, Stochastic Structure-Activity Study, Substitution, Support, Syndrome, System, Time Transducing, Transduction, U.S. Ventricles, Voltage-Gated, beta-1, {C}a$^{2+}$-Calmodulin %N 6 %P 3723--3736 %R 10.1529/biophysj.104.049973 %T A simplified local control model of calcium-induced calcium release in cardiac ventricular myocytes. %U http://dx.doi.org/10.1529/biophysj.104.049973 %V 87 %X Calcium (Ca$^2+$)-induced Ca$^2+$ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca$^2+$ release. Existing local control models of Ca$^2+$ release in which interactions between L-Type Ca$^2+$ channels (LCCs) and ryanodine-sensitive Ca$^2+$ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca$^2+$ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca$^2+$ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.

@article{Hinc_2004_3723, abstract = {Calcium ({C}a$^{2+}$)-induced {C}a$^{2+}$ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of {C}a$^{2+}$ release. Existing local control models of {C}a$^{2+}$ release in which interactions between L-Type {C}a$^{2+}$ channels (LCCs) and ryanodine-sensitive {C}a$^{2+}$ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type {C}a$^{2+}$ current in response to voltage-clamp stimuli, inactivation of LCC current with and without {C}a$^{2+}$ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Hinch, R. and Greenstein, J. L. and Tanskanen, A. J. and Xu, L. and Winslow, R. L.}, biburl = {https://www.bibsonomy.org/bibtex/2a62982d30914c50f07e4ed9ed72bd6e7/hake}, description = {The whole bibliography file I use.}, doi = {10.1529/biophysj.104.049973}, file = {Hinc_2004_3723.pdf:Hinc_2004_3723.pdf:PDF}, interhash = {d9d75b84a7e3d897b4003f8d848589f9}, intrahash = {a62982d30914c50f07e4ed9ed72bd6e7}, journal = {Biophys. J.}, key = 55, keywords = {AMP-Dependent Acid Action Adaptor Adrenergic, Algorithms, Amino Animals, Biological, Biophysics, Calcium Calcium, Cardiac, Cardiovascular, Cell Cells, Chains, Channel Channel, Channels, Comparative Complexes, Computer Conduction Contraction, Cyclic Dependent Dogs, Electrophysiology, Expression Extramural, Factors, Gating, Gene Gov't, Guinea Heart Humans, Interaction Ion Ions, Isoproterenol, Kinase, Kinases, L-Type, Long Mapping, Markov Membrane Membrane, Models, Multiprotein Muscle Myocardial Myocardium, Myocytes, N.I.H., Neurons, Non-U.S. P.H.S., Phosphatase, Phosphoprotein Phosphorylation, Pigs, Post-Translational, Potassium Potentials, Processes, Processing, Profiling, Protein Proteins, Proteome, Proteomics, QT Receptor Receptors, Regulation, Relationship, Release Research Ryanodine Ryanodine, Signal Signaling, Simulation, Stochastic Structure-Activity Study, Substitution, Support, Syndrome, System, Time Transducing, Transduction, U.S. Ventricles, Voltage-Gated, beta-1, {C}a$^{2+}$-Calmodulin}, month = Dec, number = 6, pages = {3723--3736}, pii = {biophysj.104.049973}, pmid = {15465866}, timestamp = {2009-06-03T11:21:15.000+0200}, title = {A simplified local control model of calcium-induced calcium release in cardiac ventricular myocytes.}, url = {http://dx.doi.org/10.1529/biophysj.104.049973}, volume = 87, year = 2004 }