Figure 6. Cellular AP and ionic currents for human heart failure under the influence of β-adrenergic stimulation.

Shown in (A) are cellular APs in the control (black) and human heart failure (HF - red) models after steady state pacing at BCL1000 (500 beats) and under the influence of 1μM isoproterenol, 8-fold increase in I_Na,Leak, and 10% decrease in NKA (our “nominal” HF condition). The model incorporates the Soltis-Saucerman ⁵¹ model of β-adrenergic stimulation into the human ventricular myocyte model of Grandi et al. ³⁷ as described in the Supplementary material. The APs in (A) are reproduced in both columns for ease of comparison. (B) I_CaLcurrent; (C) Na⁺/Ca²⁺ exchange current (I_NCX); (D) intracellular Ca²⁺ transient; (E) sarcoplasmic reticulum Ca²⁺ load; (F) peak (I_Na) current (note peak off scale); and (G) intracellular Na⁺ concentration. (H) Comparison between experiment and simulation for APD ^{49, 53, 75-77}, and [Na]_i ^{48, 50}. Note, both experiments and simulations were at 1 Hz (BCL 1000 ms).