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Action Potential Morphology Influences Intracellular Calcium Handling Stability and the Occurrence of Alternans
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Biophysical Journal
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2006-01
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90
Publication Issue
2
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672
Publication End
680
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Abstract
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 eigen value 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.
Citation
Jordan PN, Christini DJ. Action potential morphology influences intracellular calcium handling stability and the occurrence of alternans. Biophys J. 2006 Jan 15;90(2):672-80. doi: 10.1529/biophysj.105.071340. Epub 2005 Oct 20. PMID: 16239324; PMCID: PMC1367072.