Published online before print August 10, 2006, doi: 10.1161/01.RES.0000240542.03986.e7
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Submitted on December 8, 2005
Revised on July 10, 2006
Accepted on August 1, 2006
Spatially Discordant Alternans in Cardiac Tissue. Role of Calcium Cycling
Daisuke Sato ;
From the Department of Physics and Center for Interdisciplinary Research on Complex Systems (D.S., A.K.), Northeastern University, Boston, Mass; and Departments of Medicine (Cardiology) (Y.S., A.G., J.N.W., Z.Q.) and Physiology (A.G., J.N.W.), David Geffen School of Medicine at the University of California, Los Angeles.
* To whom correspondence should be addressed. E-mail: yshiferaw{at}mednet.ucla.edu.
Spatially discordant alternans, where the action potential duration (APD) and intracellular calcium transient (Cai) alternate with opposite phase in different regions of tissue, is known to promote wave break and reentry. However, this phenomenon is not completely understood. It is known that alternans at the cellular level can be caused by dynamical instabilities arising from either membrane voltage (Vm) attributable to steep APD restitution nor to calcium (Ca) cycling. Here, we used a mathematical model of intracellular Ca cycling, coupled with membrane ion currents, to investigate the dynamics of Vm and Cai transient alternans in an isolated cell, in 2 electrotonically coupled cells, and in 1D spatially homogeneous tissue. Our main finding is a novel instability mechanism in which the bidirectional coupling of Vm and Cai can drive the Cai transient of 2 neighboring cells to be out of phase. This instability is manifested in cardiac tissue by the dynamical formation of spatially discordant alternans. In this case, Cai transient alternans can reverse phase over a length scale of 1 cell, whereas APD alternans reverses phase over a much longer length scale set by the electrotonic coupling. We analyze this mechanism in detail and show that it is a robust consequence of experimentally established properties of the bidirectional coupling between Ca cycling and Vm dynamics. Finally, we address the experimental relevance of these findings and suggest physiological conditions under which these patterns can be observed.
Key words: discordant alternans • calcium cycling
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