Simulating Notch‐Dome Morphology of Action Potential of Ventricular Cell: How the Speeds of Positive and Negative Feedbacks on Transmembrane Voltage Can Influence the Health of a Cell?

Figures

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  Figure 1. (a) A typical morphology of ventricular AP with five distinct phases and spike-notch-dome (SND) as a significant part of an AP [2]; (b) membrane voltage of a cell can be modeled by a capacitor that is charged by ionic currents.

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  Figure 2. Graphical illustrations of (a) n(t) and h(t). (b) nh(t) for three different values of α. (c) ts against α. (d) tin against α. (e) ts and tin against α. (f) Scaling nh(t) so that it takes the maximum value of unit. In all panels, τn = 1 is fixed.

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  Figure 3. Typical realizations of (a) AP, (b) nh(t), (c) n(t), and (d) h(t), in a ventricular cell model. Here, n(t) and h(t) are the gating process. Compare these general morphologies with those in Figure 2.

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  Figure 4. Evaluation of our proposed model for simulating ventricular cell AP: (a) AP morphology generated by the model; (b) time course of nh(t); (c) time course of n(t); (d) time course of h(t).

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  Figure 5. A zoomed-in view of SND of a simulated AP and its corresponding nh. This figure justifies our approach for regulating ND in a ventricular cell model.

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  Figure 6. (a) Illustration of the effect of α on the general morphology of plateau phase of AP. We see how one can manage ND generation by regulating α. (b) Different morphologies of nh(t) generated by regulation of α. This figure validates graphically our hypothesis.

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  Figure 7. Fitting our model to the Luo-Rudy complex model: (a) simulation results: AP, nh, n, h; (b) AP of the Luo-Rudy complex model. Parameter value and goodness-of-fit measures are also reported in separate tables. The almost unit R-square shows how good our model can capture the morphology of AP.

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  Figure 8. Fitting our model to Ten Tusscher et al. [2]: (a) simulation results: AP, nh, n, h; (b) AP of the Ten Tusscher et al. complex model. Parameter value and goodness-of-fit measures are also reported in separate tables. The almost unit R-square shows how good our model can capture the morphology of AP.

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  Figure 9. AP and ND morphology of PB cell where related ionic currents are present in a cell: (a) INa + ICa + Ito + IKr + IKs + IK1 + INaCa + INaK + IbNa + IbCa + Istim; (b) INa + ICa + Ito + IKr + IKs + IK1 + INaCa + INaK + IbNa + Istim (IbCa is blocked); (c) INa + ICa + Ito + IKr + IKs + IK1 + INaCa + INaK + Istim (IbCa + IbNa are blocked). (d) INa + ICa + Ito + IKr + IKs + IK1 + INaCa + Istim (IbCa + IbNa + INaK are blocked); (e) INa + ICa + Ito + IKr + IKs + IK1 + Istim (IbCa + IbNa + INaK + INaCa are blocked); (f) INa + ICa + Ito + IKr + IKs + Istim (IbCa + IbNa + INaK + INaCa + IK1 are blocked).

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  Figure 10. AP and ND morphology of PB cell where α is adjusted on a range of 1-10. Considering regulation of ND morphology with regulation of α, our hypothesis is validated experimentally.

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  Figure 11. A typical simulation with the use of our model: (a) AP, (b) nh(t), and (c) reciprocal of nh(t) against time axis. We see how the dynamics of nh(t) reciprocal during the plateau phase is similar to AP.

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  Figure 12. Sample restitution curves generated by our model: (a) APD restitution curve; (b) conduction velocity restitution curve. The proposed model and approach can simulate this important property of ventricular cells.