Figure 1. Physiologically detailed mathematical model.

A, schematic diagram of the currents and fluxes that regulate V _m dynamics and ${\mathrm{Ca}}_{\mathrm{i}}^{2+}$ cycling. B, model of the SK channel: I _SK vs. V _m when [Ca²⁺] is 0.1, 0.5 and 1.0 μm. C, channel open probability as a function of intracellular Ca²⁺. D, inverse relationship between intracellular Ca²⁺ and the SK time constant (τ_SK2). E, open probability (P _o) vs. time when various test [Ca²⁺] pulses are applied. [Ca²⁺] was changed from 0 μm to test [Ca²⁺] for 400 ms, and then changed to 0 μm. F, transmembrane voltage plotted against time demonstrating the decrease in APD from baseline (red) to inclusion of the SK channel (black). When g _sk = 0.8 μS μF⁻¹ and EC₅₀ = 0.7 μm are chosen, the model shows 12% difference of APDs, which was shown by Hsieh et al. experimentally (Hsueh et al. 2013), by copyright permission of the American Heart Association, Inc. G, positive and negative ${\mathrm{Ca}}_{\mathrm{i}}^{2+}$→V _m coupling. H, electromechanically concordant (large APD→large Ca²⁺ transient, small APD→small Ca²⁺ transient) alternans and discordant (large APD→small Ca²⁺ transient, small APD→large Ca²⁺ transient) alternans.