Ionic current changes underlying action potential repolarization responses to physiological pacing and adrenergic stimulation in adult rat ventricular myocytes

Figures

• 

  FIGURE 1. APD50 data simulated by the mLR model (Howlett, 2022) and original LR model (Stevenson‐Cocks, 2019) compared with APD50 laboratory data (Howlett et al., 2022) during control and adrenergic stimulation conditions. Experimental data presented as mean with 95% confidence interval (1.96 × SEM) error bars. Experimental data based on N = 8. Experimental isoproterenol data based on findings from 5 nM isoproterenol dose. Figure adapted from Howlett (2022).

• 

  FIGURE 2. APD90 data simulated by the mLR model (Howlett, 2022) and original LR model (Stevenson‐Cocks, 2019) compared with APD90 laboratory data (Howlett et al., 2022) during control and adrenergic stimulation conditions. Experimental data presented as mean with 95% confidence interval (1.96 × SEM) error bars. Experimental data based on N = 8. Experimental isoproterenol data based on findings from 5 nM isoproterenol dose. Figure adapted from Howlett (2022).

• 

  FIGURE 3. Example action potential traces from experimental data (Howlett et al., 2022) and simulated AP traces from the original LR model (Stevenson‐Cocks, 2019) and the mLR model (Howlett, 2022). Traces recorded at 1, 6, and 10 Hz pacing as displayed. Figure adapted from Howlett (2022), Howlett et al. (2022), and Stevenson‐Cocks (2019).

• 

  FIGURE 4. AP amplitude simulated by the mLR model (Howlett, 2022) and original LR model (Stevenson‐Cocks, 2019) compared with laboratory data (Howlett et al., 2022) during control and adrenergic stimulation conditions. Experimental data presented as mean with 95% confidence interval (1.96 × SEM) error bars. Experimental data based on N = 8. Experimental isoproterenol data based on findings from 5 nM isoproterenol dose. Figure adapted from Howlett (2022).

• 

  FIGURE 5. Diastolic membrane potential simulated by the mLR model (Howlett, 2022) and original LR model (Stevenson‐Cocks, 2019) compared with laboratory data (Howlett et al., 2022) during control and adrenergic stimulation conditions. Experimental data presented as mean with 95% confidence interval (1.96 × SEM) error bars. Experimental data based on N = 8. Experimental isoproterenol data based on findings from 5 nM isoproterenol dose. Figure adapted from Howlett (2022).

• 

  FIGURE 6. Example steady‐state ICa current races recorded from laboratory experiments (a) (Howlett et al., 2022) and simulations from the original LR model (b) (Stevenson‐Cocks, 2019) and the mLR model (c) (Howlett, 2022). All data recorded at 1 Hz. Experimental data based on voltage‐clamp recordings. Figure adapted from Howlett (2022).

• 

  FIGURE 7. Example steady‐state Ito current traces recorded from original LR model (a) (Stevenson‐Cocks, 2019) and mLR model (b) simulations (Howlett, 2022). All data recorded at 1 Hz.

• 

  FIGURE 8. Example steady‐state IKr current traces recorded from laboratory experiments (a) (Howlett et al., 2022) and simulations from the original LR model (b) (Stevenson‐Cocks, 2019) and the mLR model (c) (Howlett, 2022). All data recorded at 1 Hz. Experimental data based on E4031‐sensitive current recordings, assumed to reflect IKr current. Original LR model Iss data were used to provide comparison with mLR model and experimental IKr data. Figure adapted from Howlett (2022).

• 

  FIGURE 9. Example steady‐state IKs current traces recorded from laboratory experiments (a) (Howlett et al., 2022) and simulations from the original LR model (b) (Stevenson‐Cocks, 2019) and the mLR model (c) (Howlett, 2022). All data recorded at 1 Hz. Experimental data based on chromanol 293b‐sensitive current recordings, assumed to reflect IKs current. Original LR model Iss data were used to provide comparison with mLR model and experimental IKs data. Figure adapted from Howlett (2022).

• 

  FIGURE 10. Example steady‐state IK1 current traces recorded from laboratory experiments (a) (Howlett et al., 2022) and simulations from the original LR model (b) (Stevenson‐Cocks, 2019) and the mLR model (c) (Howlett, 2022). All data recorded at 1 Hz. Experimental data based on BaCl2‐sensitive current recordings, assumed to reflect IK1 current. Figure adapted from Howlett (2022).

• 

  FIGURE 11. Peak ICa, Ito, IKr, IKs, and IK1 current simulated by the original LR model and the mLR model at 1–10 Hz during control conditions. Where possible, simulated peak ion current data were compared with experimental data recorded at 1 Hz from our laboratory (Howlett et al., 2022). Experimental data presented as mean with 95% confidence interval (1.96 × SEM) error bars. Experimental data based on N = 6 (peak ICa) and N = 8 (peak IKr, IKs, and IK1). Original LR model Iss data were plotted to provide comparison with mLR model and experimental IKs and IKr data. Figure adapted from Howlett (2022).

• 

  FIGURE 12. Peak ICa, Ito, IKr, IKs, and IK1 current simulated by the original LR model and the mLR model at 1–10 Hz during adrenergic stimulation. Where possible, simulated peak ion current data were compared with experimental data recorded at 1 Hz from our laboratory during 5 nM isoproterenol superfusion (Howlett et al., 2022). Experimental data presented as mean with 95% confidence interval (1.96 × SEM) error bars. Experimental data based on N = 6 (peak ICa) and N = 8 (peak IKr, IKs, and IK1). Original LR model Iss data were plotted to provide comparison with mLR model and experimental IKs and IKr data. Figure adapted from Howlett (2022).