%0 Journal Article %1 Gree_2002_2918 %A Greenstein, Joseph L %A Winslow, Raimond L %D 2002 %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, 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., Patch-Clamp Phosphatase, Phosphoprotein Phosphorylation, Pigs, Post-Translational, Potassium Potentials, Processes, Processing, Profiling, Protein Proteins, Proteome, Proteomics, QT Receptor Receptors, Regulation, Relationship, Release Research Reticulum, Ryanodine Ryanodine, Sarcoplasmic Signal Signaling, Simulation, Stochastic Structure-Activity Study, Substitution, Support, Syndrome, System, Techniques, Time Transducing, Transduction, Ventricles, {C}a$^{2+}$-Calmodulin %N 6 %P 2918--2945 %T An integrative model of the cardiac ventricular myocyte incorporating local control of Ca$^2+$ release. %U http://www.biophysj.org/cgi/content/full/83/6/2918 %V 83 %X The local control theory of excitation-contraction (EC) coupling in cardiac muscle asserts that L-type Ca$^2+$ current tightly controls Ca$^2+$ release from the sarcoplasmic reticulum (SR) via local interaction of closely apposed L-type Ca$^2+$ channels (LCCs) and ryanodine receptors (RyRs). These local interactions give rise to smoothly graded Ca$^2+$-induced Ca$^2+$ release (CICR), which exhibits high gain. In this study we present a biophysically detailed model of the normal canine ventricular myocyte that conforms to local control theory. The model formulation incorporates details of microscopic EC coupling properties in the form of Ca$^2+$ release units (CaRUs) in which individual sarcolemmal LCCs interact in a stochastic manner with nearby RyRs in localized regions where junctional SR membrane and transverse-tubular membrane are in close proximity. The CaRUs are embedded within and interact with the global systems of the myocyte describing ionic and membrane pump/exchanger currents, SR Ca$^2+$ uptake, and time-varying cytosolic ion concentrations to form a model of the cardiac action potential (AP). The model can reproduce both the detailed properties of EC coupling, such as variable gain and graded SR Ca$^2+$ release, and whole-cell phenomena, such as modulation of AP duration by SR Ca$^2+$ release. Simulations indicate that the local control paradigm predicts stable APs when the L-type Ca$^2+$ current is adjusted in accord with the balance between voltage- and Ca$^2+$-dependent inactivation processes as measured experimentally, a scenario where common pool models become unstable. The local control myocyte model provides a means for studying the interrelationship between microscopic and macroscopic behaviors in a manner that would not be possible in experiments.

@article{Gree_2002_2918, abstract = {The local control theory of excitation-contraction (EC) coupling in cardiac muscle asserts that L-type {C}a$^{2+}$ current tightly controls {C}a$^{2+}$ release from the sarcoplasmic reticulum (SR) via local interaction of closely apposed L-type {C}a$^{2+}$ channels (LCCs) and ryanodine receptors (RyRs). These local interactions give rise to smoothly graded {C}a$^{2+}$-induced {C}a$^{2+}$ release (CICR), which exhibits high gain. In this study we present a biophysically detailed model of the normal canine ventricular myocyte that conforms to local control theory. The model formulation incorporates details of microscopic EC coupling properties in the form of {C}a$^{2+}$ release units (Ca{RU}s) in which individual sarcolemmal LCCs interact in a stochastic manner with nearby RyRs in localized regions where junctional SR membrane and transverse-tubular membrane are in close proximity. The Ca{RU}s are embedded within and interact with the global systems of the myocyte describing ionic and membrane pump/exchanger currents, SR {C}a$^{2+}$ uptake, and time-varying cytosolic ion concentrations to form a model of the cardiac action potential (AP). The model can reproduce both the detailed properties of EC coupling, such as variable gain and graded SR {C}a$^{2+}$ release, and whole-cell phenomena, such as modulation of AP duration by SR {C}a$^{2+}$ release. Simulations indicate that the local control paradigm predicts stable APs when the L-type {C}a$^{2+}$ current is adjusted in accord with the balance between voltage- and {C}a$^{2+}$-dependent inactivation processes as measured experimentally, a scenario where common pool models become unstable. The local control myocyte model provides a means for studying the interrelationship between microscopic and macroscopic behaviors in a manner that would not be possible in experiments.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Greenstein, Joseph L and Winslow, Raimond L}, biburl = {https://www.bibsonomy.org/bibtex/21c95515b17e5a6dc50bd5de7a2822a0f/hake}, description = {The whole bibliography file I use.}, file = {Gree_2002_2918.pdf:Gree_2002_2918.pdf:PDF}, interhash = {5fd5f699c94fe7cf323b77bfdb1583da}, intrahash = {1c95515b17e5a6dc50bd5de7a2822a0f}, journal = {Biophys. J.}, key = 97, 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, 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., Patch-Clamp Phosphatase, Phosphoprotein Phosphorylation, Pigs, Post-Translational, Potassium Potentials, Processes, Processing, Profiling, Protein Proteins, Proteome, Proteomics, QT Receptor Receptors, Regulation, Relationship, Release Research Reticulum, Ryanodine Ryanodine, Sarcoplasmic Signal Signaling, Simulation, Stochastic Structure-Activity Study, Substitution, Support, Syndrome, System, Techniques, Time Transducing, Transduction, Ventricles, {C}a$^{2+}$-Calmodulin}, month = Dec, number = 6, pages = {2918--2945}, pmid = {12496068}, timestamp = {2009-06-03T11:21:13.000+0200}, title = {An integrative model of the cardiac ventricular myocyte incorporating local control of {C}a$^{2+}$ release.}, url = {http://www.biophysj.org/cgi/content/full/83/6/2918}, volume = 83, year = 2002 }