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Biophys. J. BioFAST: First Published April 7, 2006. doi:10.1529/biophysj.105.077214
© 2006 by the Biophysical Society.

A more recent version of this article appeared on July 1, 2006.
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BIOPHYSICAL THEORY AND MODELING

Interplay of Ryanodine Receptor Distribution and Calcium Dynamics

Leighton T Izu 1*, Shawn A Means 2, John N Shadid 2, Ye Chen-Izu 1 and C. William Balke 1

1 University of Kentucky
2 Sandia National Laboratories

* To whom correspondence should be addressed. E-mail: leightonizu{at}uky.edu.

Submitted on November 7, 2005
Revised on December 15, 2005
Accepted on 13 March 2006


  Abstract
Spontaneously generated calcium (Ca2+) waves can trigger arrhythmias in ventricular and atrial myocytes. Yet, Ca2+ waves also serve the physiological function of mediating global Ca2+ increase and muscle contraction in atrial myocytes. We examine the factors that influence Ca2+ wave initiation by mathematical modeling and large-scale computational (supercomputer) simulations. An important finding is the existence of a strong coupling between the ryanodine receptor (RyR2) distribution and Ca2+ dynamics. Even modest changes in the RyR2 spacing profoundly affect the probability of Ca2+ wave initiation. As a consequence of this finding, we suggest that there is a feedback from the contractile system to the Ca2+ control system and this dynamical interplay could contribute to the increased incidence of arrhythmias during heart failure.

Key Words: arrhythmia, calcium sparks, calcium waves, cardiac, excitation-contraction coupling, mathematical modeling




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Copyright © 2006 by the Biophysical Society.