HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/3/H1154    most recent 00168.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Bondarenko, V. E. Articles by Rasmusson, R. L. Search for Related Content PubMed PubMed Citation Articles by Bondarenko, V. E. Articles by Rasmusson, R. L.

A model of graded calcium release and L-type Ca²⁺ channel inactivation in cardiac muscle

Department of Physiology and Biophysics, University at Buffalo, State University of New York, Buffalo, New York 14214

Submitted 20 February 2003 ; accepted in final form 6 November 2003

We have developed a model of Ca²⁺ handling in ferret ventricular myocytes. This model includes a novel L-type Ca²⁺ channel, detailed intracellular Ca²⁺ movements, and graded Ca²⁺-induced Ca²⁺ release (CICR). The model successfully reproduces data from voltage-clamp experiments, including voltage- and time-dependent changes in intracellular Ca²⁺ concentration ([Ca²⁺]_i), L-type Ca²⁺ channel current (I_CaL) inactivation and recovery kinetics, and Ca²⁺ sparks. The development of graded CICR is critically dependent on spatial heterogeneity and the physical arrangement of calcium channels in opposition to ryanodine-sensitive release channels. The model contains spatially distinct subsystems representing the subsarcolemmal regions where the junctional sarcoplasmic reticulum (SR) abuts the T-tubular membrane and where the L-type Ca²⁺ channels and SR ryanodine receptors (RyRs) are localized. There are eight different types of subsystems in our model, with between one and eight L-type Ca²⁺ channels distributed binomially. This model exhibits graded CICR and provides a quantitative description of Ca²⁺ dynamics not requiring Monte-Carlo simulations. Activation of RyRs and release of Ca²⁺ from the SR depend critically on Ca²⁺ entry through L-type Ca²⁺ channels. In turn, Ca²⁺ channel inactivation is critically dependent on the release of stored intracellular Ca²⁺. Inactivation of I_CaL depends on both transmembrane voltage and local [Ca²⁺]_i near the channel, which results in distinctive inactivation properties. The molecular mechanisms underlying many I_CaL gating properties are unclear, but [Ca²⁺]_i dynamics clearly play a fundamental role.

myocytes; computer simulation; inactivation; calcium-induced calcium release; excitation-contraction coupling

This article has been cited by other articles:

				J. G. Restrepo, J. N. Weiss, and A. Karma Calsequestrin-Mediated Mechanism for Cellular Calcium Transient Alternans Biophys. J., October 15, 2008; 95(8): 3767 - 3789. [Abstract] [Full Text] [PDF]

				G. S. B. Williams, M. A. Huertas, E. A. Sobie, M. S. Jafri, and G. D. Smith Moment Closure for Local Control Models of Calcium-Induced Calcium Release in Cardiac Myocytes Biophys. J., August 15, 2008; 95(4): 1689 - 1703. [Abstract] [Full Text] [PDF]

				G. S. B. Williams, M. A. Huertas, E. A. Sobie, M. S. Jafri, and G. D. Smith A Probability Density Approach to Modeling Local Control of Calcium-Induced Calcium Release in Cardiac Myocytes Biophys. J., April 1, 2007; 92(7): 2311 - 2328. [Abstract] [Full Text] [PDF]

				T. Namiki, R. W. Joyner, and M. B. Wagner Developmental changes in time course of recovery from inactivation in L-type calcium currents of rabbit ventricular myocytes Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H295 - H303. [Abstract] [Full Text] [PDF]

				G. T. Lines, J. B. Sande, W. E. Louch, H. K. Mork, P. Grottum, and O. M. Sejersted Contribution of the Na+/Ca2+ Exchanger to Rapid Ca2+ Release in Cardiomyocytes Biophys. J., August 1, 2006; 91(3): 779 - 792. [Abstract] [Full Text] [PDF]

				J. L. Greenstein, R. Hinch, and R. L. Winslow Mechanisms of Excitation-Contraction Coupling in an Integrative Model of the Cardiac Ventricular Myocyte Biophys. J., January 1, 2006; 90(1): 77 - 91. [Abstract] [Full Text] [PDF]

				M. Inoue and J. H. B. Bridge Variability in Couplon Size in Rabbit Ventricular Myocytes Biophys. J., November 1, 2005; 89(5): 3102 - 3110. [Abstract] [Full Text] [PDF]

				V. E. Bondarenko, G. P. Szigeti, G. C. L. Bett, S.-J. Kim, and R. L. Rasmusson Computer model of action potential of mouse ventricular myocytes Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1378 - H1403. [Abstract] [Full Text] [PDF]