A simple numerical model of calcium spark formation and detection in cardiac myocytes.
G. Smith, J. Keizer, M. Stern, W. Lederer, and H. Cheng.
Biophys. J. 75 (1): 15--32 (July 1998)

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.

URL: http://www.biophysj.org/cgi/content/full/75/1/15
search on: Google Scholar Microsoft Bing WorldCat BASE

This publication has not been reviewed yet.

rating distribution

average user rating0.0 out of 5.0 based on 0 reviews

Please log in to take part in the discussion (add own reviews or comments).

@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
}

%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.

BibSonomy

A simple numerical model of calcium spark formation and detection in cardiac myocytes.
G. Smith, J. Keizer, M. Stern, W. Lederer, and H. Cheng.
Biophys. J. 75 (1): 15--32 (July 1998)

Tags

Users

Comments and Reviews

Cite this publication

BibSonomy

A simple numerical model of calcium spark formation and detection in cardiac myocytes.G. Smith, J. Keizer, M. Stern, W. Lederer, and H. Cheng. Biophys. J. 75 (1): 15--32 (July 1998)

Tags

Users

Comments and Reviews

Cite this publication

A simple numerical model of calcium spark formation and detection in cardiac myocytes.
G. Smith, J. Keizer, M. Stern, W. Lederer, and H. Cheng.
Biophys. J. 75 (1): 15--32 (July 1998)