Action potential morphology influences intracellular calcium handling stability and the occurrence of alternans
Peter N Jordan 1 and David J Christini 2*
1 Weill Graduate School of Medical Sciences of Cornell University
2 Weill Medical College of Cornell University
* To whom correspondence should be addressed. E-mail: dchristi{at}med.cornell.edu.
Submitted on July 22, 2005
Revised on August 19, 2005
Accepted on 28 September 2005
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Abstract |
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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 non-alternating Ca2+ transients to stable alternating Ca2+ transients. This bifurcation occurs as the alternans eigenvalue of the system changes from absolute value smaller than 1 to absolute value greater than 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.
Key Words:
restitution curve, stability analysis
