Session SA3.6

Mathematical Modeling of Dynamic Subcellular Calcium Alternans

SA Gaeta, G Bub, GW Abbott, DJ Christini*

Weill Cornell Medical College
New York, NY, USA

Cardiac repolarization alternans is an arrhythmogenic electrophysiological pattern that occurs at the myocyte level as a beat-to-beat alternation in action potential morphology and intracellular calcium concentration. Recently, subcellular alternans, in which adjacent regions of a myocyte undergo out-of-phase alternations in calcium concentration, have been observed. We have used a spatially extended mathematical model, with distinct representations of the calcium handling dynamics of each subcellular sarcomere, to study this behavior. Our modeling findings suggest that a dynamical pattern-formation mechanism, rather than pre-existing structural heterogeneity as posited by previous studies, can initiate subcellular alternans. Importantly, our modeling predictions are consistent with experiments we have performed in isolated cardiac myocytes, thereby supporting a dynamical mechanism as a cause of subcellular alternans in real cardiac myocytes.

(Abstract Control Number: 94)