Figure 1.
Measurement of Rm using voltage clamp pulses to determine the voltage-current (V-I) relationship.
(A): Timing of onset of clamp pulses during different phases of the TNNP ventricle model AP are indicated by the stars. (B): Application of voltage clamp pulses 10 mV above (red curve) and below (blue curve) the membrane voltage at fifth point in the previous panel. (C): Membrane currents (Im) corresponding to clamp pulses in panel B. (D): Vm -Im graph for the calculation of membrane resistance.
Table 1.
Maximum and Minimum value of parameters.
Table 2.
Dependence of the Number of potential solutions on accuracy.
Figure 2.
AP and Rm for two sets of parameters.
(A): APs produced by two sets of parameters (shown in Table 3) for the TNNP model in single cell (SC) and tissue (Tissue) simulations. (B) Stars indicate voltage clamp control points as defined in Fig.A. The AP is shown in black curve. (C) Rm calculated at nine points during the AP for parameter set 1 and 2. Red and blue curves show membrane resistances calculated for parameter sets 1 and 2 respectively. The Y axis is logarithmic.
Table 3.
Two parameter sets for the TNNP ventricle model showing similar AP [3].
Figure 3.
The red dashed curve shows the single cell AP for TNNP model as published [22]. the blue dashed-dotted curve shows the single cell AP waveform generated by genetic algorithm after fitiing AP+Rm. Membrane resistance was evaluated and fitted at three different voltage points as indicated by the markers.
Figure 4.
Model-to-model fit: TNNP ventricle model fitted to the IMW ventricular model.
(A): The TNNP (red) was fit to the IMW model (green), using only the AP (blue), or the AP+Rm (magenta) measured at three different points (black star markers). Orange square markers represent the corresponding voltage points in AP+Rm fit curve obtained from genetic algorithm (B): Plot of normalized average and SD of parameters from the pareto set generated from the genetic algorithm output from AP only (gray) and AP+Rm fits (black).
Figure 5.
Effect of changing tissue coupling with the two parameters sets of TNNP model.
Red and blue curve show the APs for parameter set 1 and 2 for TNNP model. The green curve shows the AP for parameter set 2 when the coupling has been decreased by a factor of 10. The purple dotted curve shows the curve for parameter set1 with the coupling increased by a factor of 10.
Figure 6.
Fit of UCLA rabbit ionic model to experimentally recorded AP data set 1.
(A) The UCLA rabbit ionic model (red) was fit to experimental data set 2 (green) using just the AP (blue), and the AP+Rm (magenta) measured at 5 different points (black star markers). Orange square markers represent the corresponding voltage points in AP+Rm fit curve obtained from genetic algorithm. (B): Plot of normalized average and SD of parameters from the pareto set generated from the GA output from AP only and AP+Rm fits. Bars show normalized averages with SD for the optimal values of particular parameters with AP only fit (grey) and AP+Rm fit (black).
Figure 7.
Fit of UCLA rabbit model to experimentally recorded AP data set 2.
(A): The base UCLA rabbit ionic model (red) was fit to experimental data set 2 (green) using just the AP (blue), and the AP+Rm (magenta) measured at 4 different points (black stars). Orange square markers represent the corresponding voltage points in AP+Rm fit curve obtained from genetic algorithm. (B): Plot of normalized average and SD of parameters from the Pareto set generated from the genetic algorithm output from AP only and AP+Rm fits. Bars show normalized averages with SD for the optimal values of particular parameters with AP (grey) and AP+Rm fits (black).
Figure 8.
Error for fitting the TNNP to the IMW model (TNNP-IMW), and fitting the UCLA rabbit model to experimental data sets 1 (UCLA-Expt1) and 2 (UCLA-Expt2) are shown. Grey bars shows MSE for fitting AP only while black bars show the MSE of fitting AP+Rm.(A). MSE of AP voltage normalized by square of height of AP. (B) MSE of Rm normalized by square of actual membrane resistance at particular voltage point.
Table 4.
Rm measured 5 ms and 10 ms after start of clamp pulse.