Action potential morphology influences intracellular calcium handling stability and the occurrence of alternans.
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.
Jordan
Peter N
PN
Department of Physiology and Biophysics, Weill Graduate School of Medical Sciences of Cornell University, New York, New York, 10021, USA.
Christini
David J
DJ
D000200:Action Potentials; D000818:Animals; D001703:Biophysics / Q000379:methods*; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D006329:Heart Conduction System; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials; D015233:Models, Statistical; D008962:Models, Theoretical; D032342:Muscle Cells / Q000378:metabolism; D011817:Rabbits; D012680:Sensitivity and Specificity; D013997:Time Factors
D002118:Calcium