Panel A: A curve plot with data points showing the dependence of peak NaV current amplitude on pulse number for each NaV1.2+FGF-A combination at a frequency of 5 hertz. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents the normalized NaV current, ranging from 0 to 1. Different colored curves represent different FGF-A combinations: 11A (green), 12A (purple), 13A (blue), and 14A (red). Panel B: A curve plot with data points showing the predicted reduction during 10 pulse trains applied at 5 hertz for each NaV1.2+FGF-A combination based on rate constants for an allosteric LTI model. The x-axis represents the pulse number in the train, ranging from 0 to 10. The y-axis represents the normalized NaV current, ranging from 0 to 1. Different colored curves represent different FGF-A combinations: 11A (green), 12A (purple), 13A (blue), and 14A (red). Panel C: A curve plot with data points showing experimentally measured fractional amplitudes of P10-evoked current as a function of train frequency. The x-axis represents the train frequency in hertz, ranging from 0.1 to 100. The y-axis represents the fractional NaV current, ranging from 0 to 1. Different colored curves represent different FGF-A combinations: 11A (green), 12A (purple), 13A (blue), and 14A (red). Panel D: A curve plot with data points showing calculated P10-evoked current amplitudes based on the allosteric LTI model with fit as in panel C. The x-axis represents the train frequency in hertz, ranging from 0.1 to 100. The y-axis represents the fractional NaV current, ranging from 0 to 1. Different colored curves represent different FGF-A combinations: 11A (green), 12A (purple), 13A (blue), and 14A (red). Panel E: A bar graph showing the mean, standard deviation, and individual values for fitted f50 for different NaV1.2+FGF-A pairings. The x-axis represents different FGF-A combinations: 14A, 13A, 12A, and 11A. The y-axis represents the tuning frequency in hertz, ranging from 1 to 100. Panel F: A scatter plot showing f50 values plotted versus slow recovery time constant for different FGF-As. The x-axis represents the slow recovery time constant in milliseconds, ranging from 100 to 1000. The y-axis represents the tuning frequency in hertz, ranging from 1 to 100. Red circles represent mean f50 values obtained from fits to individual cells used in panel C. Open triangles represent f50 values from fits of the calculated LTI model values in panel D.
Different FGF-A homologues differentially tune firing frequency. (A) Replot of 5 Hz train data (Fig. 11, A1–D1) comparing dependence of peak NaV current amplitude on pulse number for each NaV1.2+FGF-A combination. (B) Calculation of predicted reduction during 10-pulse trains applied at 5 Hz for each NaV1.2+FGF-A combination based on rate constants for allosteric LTI model shown in Table 6. (C) Experimentally measured fractional amplitudes of P10-evoked current as a function of train frequency. Lines correspond to best fits of the IP10(f) = exp(−f/f50), where f is the train frequency and f50 is the frequency at which fractional peak NaV is reduced to 0.5. Dotted line indicates level of half reduction of peak current. (D) Calculated P10-evoked current amplitudes based on the allosteric LTI model with fit as in D. (E) Plot of mean, SD, and individual values for fitted f50 for different NaV1.2+FGF-A pairings. Comparison of distributions used an ANOVA test followed by Tukey’s multiple comparisons correction. For 14A vs. 13A, ****P < 0.0001; for 14A vs. 12A, ****P < 0.0001; for 14A vs. 11A, ****P < 0.0001; for 13A vs. 12A, ****P < 0.0001; for 13A vs. 11A, ****P < 0.0001; for 12A vs. 11A, P = 0.008. (F)f50 values are plotted versus slow recovery time constant for different FGF-As. Red: mean f50 values obtained from fits to individual cells used in panel C. Open symbols: f50 values from fits of the calculated LTI model values (panel D). The fitted line has no physical meaning but highlights the trend of the f50 vs. τs relationship. **P < 0.01.