Abstract:
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A variety of cardiac arrhythmias are initiated by a focal excitation that disrupts the regular beating of the heart. In some
cases it is known that these excitations are due to calcium (Ca) release from the sarcoplasmic reticulum (SR) via propagating
subcellular Ca waves. However, it is not understood what are the physiological factors that determine the timing of these
excitations at both the subcellular and tissue level. In this paper we apply analytic and numerical approaches to determine
the timing statistics of spontaneous Ca release (SCR) in a simplified model of a cardiac myocyte. In particular, we compute
the mean first passage time (MFPT) to SCR, in the case where SCR is initiated by spontaneous Ca sparks, and demonstrate
that this quantity exhibits either an algebraic or exponential dependence on system parameters. Based on this analysis we
identify the necessary requirements so that SCR occurs on a time scale comparable to the cardiac cycle. Finally, we study
how SCR is synchronized across many cells in cardiac tissue, and identify a quantitative measure that determines the relative
timing of SCR in an ensemble of cells. Using this approach we identify the physiological conditions so that cell-to-cell
variations in the timing of SCR is small compared to the typical duration of an SCR event. We argue further that under these
conditions inward currents due to SCR can summate and generate arrhythmogenic triggered excitations in cardiac tissue. |