A: Simulated CASQ2 reduction in virtual mouse model membrane voltage (top) and intracellular Ca2+ transients (bottom) are shown during 2 Hz pacing. (i) Control with 1 µM simulated isoprenaline, (ii) CASQ2 25% reduction, (iii) 50% reduction, and (iv) 75% reduction. Red arrows indicate spontaneous triggers. Cells were paced for 2 minutes. Last 4 seconds are shown in the figure. (B: Space-time representation generated from the 1-dimensional coupled rabbit tissue model harboring 75% reduction in CASQ2 at a frequency of 2 Hz. (i) Voltage time course and (ii) corresponding calcium transient. Red arrows indicate spontaneous delayed afterdepolarizations, triggered action potentials, and Ca2+ transients. Cai = intracellular calcium concentration; CASQ2 = cardiac calsequestrin 2; Vm= membrane voltage.