Panel A shows a pulse train protocol schematic and representative sodium current traces for WT and FGF14A, FGF13A, FGF12A, and FGF11A constructs, illustrating responses during repetitive stimulation and subsequent recovery intervals with scale bars for current and time. Panel B shows recovery curves as data points with fitted curves of normalized current ratio P2 divided by P1 versus recovery time in milliseconds for WT under different stimulation frequencies. Panel C shows recovery curves as data points with fitted curves of normalized current ratio P2 divided by P1 versus recovery time in milliseconds for WT coexpressed with each FGF-A isoform across different frequencies. Panel D shows plots of fractional amplitudes of fast and slow recovery components with y-axis fractional amplitude and x-axis train frequency in hertz, including individual data points and mean values. Panel E shows plots of recovery time constants with y-axis recovery time in milliseconds and x-axis train frequency in hertz, comparing fast and slow components across constructs with individual data points and mean values.
Use-dependent accumulation in LTI produced by pulse trains varies among FGF-A isoforms. (A) A 10-pulse train (10P) of 10-ms depolarizations to 0 mV applied at different frequencies (5–40 Hz, top panel) followed by recovery intervals at −80 mV from 0.1 ms to 5 s preceding another 25-ms step to 0 mV (P2) was used to examine recovery from inactivation mediated by FGF-A isoforms. Examples of INa traces at 5 Hz pulse trains for NaV1.2 (WT) alone and coexpressed with each FGF-A isoform are shown. Red traces show INa current during P2 steps following recovery intervals of 1, 10, 100, and 1,000 ms. (B and C) Averaged time course of fractional recovery following a 10-pulse train at different frequencies for (B) WT alone and (C) in presence of each A-type FGF isoform, as indicated. Normalized IPEAK (P2 amp/P1 amp) from protocol, as in A, was used to assess recovery from inactivation following a single pulse (1P), or following 5 or 40 Hz 10-pulse trains. Lines show single exponential fits to data points (mean ± SD). Colored solid lines correspond to exponential fit of recovery from inactivation following a single step (1P) for NaV1.2 alone (WT) (black) and WT coexpressed with FGF14A (red), FGF13A (blue), FGF12A (magenta), or FGF11A (green) in the corresponding panels. (D) Dependence of fractional amplitude of fast and slow recovery component on frequency of pulse trains for each construct along with values for individual cells. Fast and slow recovery components following a single step (1P) are plotted at “0 Hz.” Data are expressed as mean ± SD (Table S6). (E) Dependence of fast and slow recovery time constants on frequency of pulse trains for each construct along with values for individual cells, with recovery time constants following a single step (1P) plotted at “0 Hz.” Dotted line plots fast recovery for NaV1.2 alone. Data are expressed as mean ± SD (Table S6).