Figure S2.
Panel A1: A curve plot with data points showing normalized INa values during pulse trains for NaV1.2 IQM with FGF14A. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases. Panel A2: A curve plot with data points showing calculated normalized INa values during pulse trains for NaV1.2_IQM with FGF14A based on the allosteric LTI model. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases. Panel B1: A curve plot with data points showing normalized INa values during pulse trains for NaV1.2 IQM with FGF13A. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases. Panel B2: A curve plot with data points showing calculated normalized INa values during pulse trains for NaV1.2 IQM with FGF13A based on the allosteric LTI model. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases. Panel C1: A curve plot with data points showing normalized INa values during pulse trains for NaV1.2 IQM with FGF12A. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases. Panel C2: A curve plot with data points showing calculated normalized INa values during pulse trains for NaV1.2 IQM with FGF12A based on the allosteric LTI model. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases. Panel D1: A curve plot with data points showing normalized INa values during pulse trains for NaV1.2 IQM with FGF11A. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases. Panel D2: A curve plot with data points showing calculated normalized INa values during pulse trains for NaV1.2 IQM with FGF11A based on the allosteric LTI model. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents normalized INa, ranging from 0.0 to 1.0. Different curves represent different frequencies (1 hertz, 2 hertz, 5 hertz, 10 hertz, 20 hertz, 40 hertz), with each curve showing a decrease in normalized INa as the pulse number increases.
The allosteric LTI model with fast inactivation removed is consistent with experimentally observed use-dependent changes in Na V 1.2 availability during trains. (A1) A 10-pulse train of 10-ms depolarizations to 0 mV applied at different frequencies (1–40 Hz) was used to examine the cumulative inactivation of NaV1.2_IQM+FGF14A current as shown in Fig. S1. (A2) Predicted diminution during a 10-pulse train of depolarizations was calculated based on the allosteric LTI model for FGF14A for channels with fast inactivation removed. (B1 and B2) Measured and calculated diminution during pulse trains for NaV1.2_IQM+FGF13A currents. (C1 and C2) Measured and calculated diminution for NaV1.2_IQM+FGF12A currents. (D1 and D2) Measured and calculated diminution for NaV1.2_IQM+FGF11A currents.