Buffering and total calcium levels determine the presence of oscillatory regimes in cardiac cells

摘要

In cardiac cells, calcium plays a very important role. An increase in calcium levels is the trigger used by the cell to initiate contraction. Besides, calcium modulates several transmembrane currents, affecting the cell transmembrane potential. Thus, dysregulations in calcium handling have been associated with the appearance of arrhythmias. Often, this dysregulation results in the appearance of periodic calcium waves or global oscillations, providing a pro-arrhythmic substrate. In this paper, we study the onset of calcium oscillations in cardiac cells using both a detailed subcellular model of calcium dynamics and a minimal model that takes into account the essential ingredients of the calcium toolkit. Both reproduce the main experimental results and link this behavior with the presence of different steady-state solutions and bifurcations that depend on the total amount of calcium in the cell and in the level of buffering present. We expect that this work will help to clarify the conditions under which calcium oscillations appear in cardiac myocytes and, therefore, will represent a step further in the understanding of the origin of cardiac arrhythmias.