Instability in the intracellular Ca2+ handling system leading to Ca2+ alternans is hypothesized to be an underlying cause of electrical alternans. The highly coupled nature of membrane voltage and Ca2+ regulation suggests that there should be reciprocal effects of membrane voltage on the stability of the Ca2+ handling system. We investigated such effects using a mathematical model of the cardiac intracellular Ca2+ handling system. We found that the morphology of the action potential has a significant effect on the stability of the Ca2+ handling system at any given pacing rate, with small changes in action potential morphology resulting in a transition from stable nonalternating Ca2+ transients to stable alternating Ca2+ transients. This bifurcation occurs as the alternans eigenvalue of the system changes from absolute value <1 to absolute value >1. These results suggest that the stability of the intracellular Ca2+ handling system and the occurrence of Ca2+ alternans are not dictated solely by the Ca2+ handling system itself, but are also modulated to a significant degree by membrane voltage (through its influence on sarcolemmal Ca2+ currents) and, therefore, by all ionic currents that affect membrane voltage. © 2006 by the Biophysical Society.
CITATION STYLE
Jordan, P. N., & Christini, D. J. (2006). Action potential morphology influences intracellular calcium handling stability and the occurrence of alternans. Biophysical Journal, 90(2), 672–680. https://doi.org/10.1529/biophysj.105.071340
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