Panel A1 shows a curve plot of experimentally measured changes in peak INa during a 10 pulse train applied at various frequencies for NaV1.2 plus FGF14A. The x-axis represents the pulse number in the train, and the y-axis represents the normalized INa. Panel A2 shows a curve plot of calculated diminution of NaV1.2 plus FGF14A availability during 10 pulse trains applied at the indicated frequencies based on parameters for inactivation onset and recovery. The x-axis represents the pulse number in the train, and the y-axis represents the normalized availability. Panel A3 shows a curve plot of experimentally measured and calculated recovery from inactivation for a single depolarization and following a 10 pulse train at 5 Hz and 40 Hz for NaV1.2+FGF14A. The x-axis represents the recovery time in milliseconds, and the y-axis represents the ratio of peak INa. Panel A4 shows a curve plot of experimentally measured and calculated fractional As for 1P recovery and then at the end of each of 10 pulse trains applied at the indicated frequencies, with lines reflecting predictions from allosteric LTI model and standard LTI model. The x-axis represents the train frequency in Hz, and the y-axis represents the fractional As. Panels B1 to B4, C1 to C4, and D1 to D4 follow the same structure as panels A1 to A4 but are determined for parameters derived from NaV1.2 plus FGF13A, NaV1.2 plus FGF12A, and NaV1.2 plus FGF11A, respectively.
Impact of FGF-A homologues on use-dependent changes in Na V availability. (A1) Experimentally measured changes in peak INa during a 10-pulse train applied at the indicated frequencies for NaV1.2+FGF14A. (A2) Calculated diminution of NaV1.2+FGF14A availability during 10-pulse trains applied at the indicated frequencies based on parameters for inactivation onset and recovery determined in accordance with modified LTI model (Scheme 3 and Table 6). (A3) Experimentally measured (points) and calculated recovery (lines) from inactivation for a single depolarization (1P) and also following a 10-pulse train at 5 Hz (blue) and a 10-pulse train at 40 Hz (red) for NaV1.2+FGF14A. (A4) Experimentally measured (points) and calculated fractional As for 1P recovery and then at the end of each of 10-pulse trains applied at the indicated frequencies with lines reflecting predictions from allosteric LTI model (red) and standard LTI model (dashed blue). (B1–B4) As for panels in A, but determined for parameters derived from NaV1.2+FGF13A. (C1–C4) Calculated use dependence based on parameters derived from NaV1.2+FGF12A. (D1–D4) Calculated use-dependence based on parameters derived from NaV1.2+FGF11A.