Action potential morphology influences intracellular calcium handling stability and the occurrence of alternans

作者：Jordan PN; Christini DJ^*

来源：Biophysical Journal, 2006, 90(2): 672-680.

DOI：10.1529/biophysj.105.071340

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.

• 出版日期2006-1