%0 Journal Article %1 Smit_1998_15 %A Smith, G. D. %A Keizer, J. E. %A Stern, M. D. %A Lederer, W. J. %A Cheng, H. %D 1998 %J Biophys. J. %K 9649364 ATPase, Acid, Agents, Agonists, Algorithms, Analysis, Aniline Animal Animals, Anisotropy, Anoxia, Biological, Biophysics, Blockers, Bone Bones, Calcium Calcium, Cardiovascular, Cattle, Cell Cells, Channel Channel, Channels, Chelating Clonazepam, Compounds, Confocal, Contraction, Cultured, Cytosol, Dietary Dyes, Dynamics, Egtazic Electric Electrophysiology, Exchanger, Feed, Feedback, Female, Fluorescence, Fluorescent Gov't, Heart, In Indoles, Ion Kinetics, Linear Male, Meat, Membrane Microscopy, Minerals, Mitochondria, Models, Myocardial Myocardium, Non-U.S. Nonlinear Oxygen, P.H.S., Patch-Clamp Potentials, Proteins, Pyrroles, Rats, Receptor Red, Regression Release Research Reticulum, Rumen, Ruthenium Ryanodine Sarcoplasmic Signal Signaling, Size, Sodium-Calcium Soybeans, Sprague-Dawley, Stimulation, Support, Techniques, Transduction, Transport, U.S. Vitro, Wistar, Xanthenes, and {C}a$^{2+}$-Transporting %N 1 %P 15--32 %T A simple numerical model of calcium spark formation and detection in cardiac myocytes. %U http://www.biophysj.org/cgi/content/full/75/1/15 %V 75 %X The elementary events of excitation-contraction coupling in heart muscle are Ca$^2+$ sparks, which arise from one or more ryanodine receptors in the sarcoplasmic reticulum (SR). Here a simple numerical model is constructed to explore Ca$^2+$ spark formation, detection, and interpretation in cardiac myocytes. This model includes Ca$^2+$ release, cytosolic diffusion, resequestration by SR Ca$^2+$-ATPases, and the association and dissociation of Ca$^2+$ with endogenous Ca$^2+$-binding sites and a diffusible indicator dye (fluo-3). Simulations in a homogeneous, isotropic cytosol reproduce the brightness and the time course of a typical cardiac Ca$^2+$ spark, but underestimate its spatial size (approximately 1.1 micron vs. approximately 2.0 micron). Back-calculating Ca$^2+$i by assuming equilibrium with indicator fails to provide a good estimate of the free Ca$^2+$ concentration even when using blur-free fluorescence data. A parameter sensitivity study reveals that the mobility, kinetics, and concentration of the indicator are essential determinants of the shape of Ca$^2+$ sparks, whereas the stationary buffers and pumps are less influential. Using a geometrically more complex version of the model, we show that the asymmetric shape of Ca$^2+$ sparks is better explained by anisotropic diffusion of Ca$^2+$ ions and indicator dye rather than by subsarcomeric inhomogeneities of the Ca$^2+$ buffer and transport system. In addition, we examine the contribution of off-center confocal sampling to the variance of spark statistics.

@article{Smit_1998_15, abstract = {The elementary events of excitation-contraction coupling in heart muscle are {C}a$^{2+}$ sparks, which arise from one or more ryanodine receptors in the sarcoplasmic reticulum (SR). Here a simple numerical model is constructed to explore {C}a$^{2+}$ spark formation, detection, and interpretation in cardiac myocytes. This model includes {C}a$^{2+}$ release, cytosolic diffusion, resequestration by SR {C}a$^{2+}$-ATPases, and the association and dissociation of {C}a$^{2+}$ with endogenous {C}a$^{2+}$-binding sites and a diffusible indicator dye (fluo-3). Simulations in a homogeneous, isotropic cytosol reproduce the brightness and the time course of a typical cardiac {C}a$^{2+}$ spark, but underestimate its spatial size (approximately 1.1 micron vs. approximately 2.0 micron). Back-calculating [{C}a$^{2+}$]i by assuming equilibrium with indicator fails to provide a good estimate of the free {C}a$^{2+}$ concentration even when using blur-free fluorescence data. A parameter sensitivity study reveals that the mobility, kinetics, and concentration of the indicator are essential determinants of the shape of {C}a$^{2+}$ sparks, whereas the stationary buffers and pumps are less influential. Using a geometrically more complex version of the model, we show that the asymmetric shape of {C}a$^{2+}$ sparks is better explained by anisotropic diffusion of {C}a$^{2+}$ ions and indicator dye rather than by subsarcomeric inhomogeneities of the {C}a$^{2+}$ buffer and transport system. In addition, we examine the contribution of off-center confocal sampling to the variance of spark statistics.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Smith, G. D. and Keizer, J. E. and Stern, M. D. and Lederer, W. J. and Cheng, H.}, biburl = {https://www.bibsonomy.org/bibtex/2f49363af4da096ec89d489f6ae8c4925/hake}, description = {The whole bibliography file I use.}, file = {Smit_1998_15.pdf:Smit_1998_15.pdf:PDF}, interhash = {5784aca2aaa87ec04645e089c003d1c2}, intrahash = {f49363af4da096ec89d489f6ae8c4925}, journal = {Biophys. J.}, key = 76, keywords = {9649364 ATPase, Acid, Agents, Agonists, Algorithms, Analysis, Aniline Animal Animals, Anisotropy, Anoxia, Biological, Biophysics, Blockers, Bone Bones, Calcium Calcium, Cardiovascular, Cattle, Cell Cells, Channel Channel, Channels, Chelating Clonazepam, Compounds, Confocal, Contraction, Cultured, Cytosol, Dietary Dyes, Dynamics, Egtazic Electric Electrophysiology, Exchanger, Feed, Feedback, Female, Fluorescence, Fluorescent Gov't, Heart, In Indoles, Ion Kinetics, Linear Male, Meat, Membrane Microscopy, Minerals, Mitochondria, Models, Myocardial Myocardium, Non-U.S. Nonlinear Oxygen, P.H.S., Patch-Clamp Potentials, Proteins, Pyrroles, Rats, Receptor Red, Regression Release Research Reticulum, Rumen, Ruthenium Ryanodine Sarcoplasmic Signal Signaling, Size, Sodium-Calcium Soybeans, Sprague-Dawley, Stimulation, Support, Techniques, Transduction, Transport, U.S. Vitro, Wistar, Xanthenes, and {C}a$^{2+}$-Transporting}, month = Jul, number = 1, pages = {15--32}, pmid = {9649364}, timestamp = {2009-06-03T11:21:31.000+0200}, title = {A simple numerical model of calcium spark formation and detection in cardiac myocytes.}, url = {http://www.biophysj.org/cgi/content/full/75/1/15}, volume = 75, year = 1998 }