Estimating the probabilities of rare arrhythmic events in multiscale computational models of cardiac cells and tissue
(a) Normalized peak LCC (triangles) and RyR (circles) flux when the membrane was stepped to test potentials between -20 and 40 mV. (b) Excitation-contraction coupling gain, defined as the ratio of the normalized peak RyR to LCC Ca2+ flux at each test potential. (c) Representative action potentials and (d) [Ca2+]i transients under control conditions (solid black), with 50% IK1 inhibition (dashed black), with β-adrenergic stimulation (solid red) conditions, and with β-adrenergic stimulation and 50% IK1 inhibition (dashed red). (e) Cell-wide SR Ca2+ leak rate via RyRs at varying SR Ca2+ loads in the baseline model. The dotted line indicates the lowest SR Ca2+ load tested that exhibited spontaneous Ca2+ waves. (f) Example linescan plot showing a Ca2+ wave under β-adrenergic stimulation.