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.
%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
}