Figure 10.
Evaluation of the impact of slow and fast recovery from inactivation on use-dependent diminution of peak Nav amplitude.(A) The basic stimulation protocol for calculation of state occupancies, use-dependent peak current diminution, and 1P/10P recovery time course. From a −80 mV holding potential, a 10-Hz train of 20 5-ms steps to 0 mV was used to produce channel activation and inactivation. This corresponds to a 95-ms recovery interval between steps to 0 mV. Red triangles indicate time points before depolarization and green, after full inactivation. For calculations in B–D, fractional inactivation before P1 is assumed to be 0.05, with inactivated states split evenly between fast and slow recovery pathways. (B) Calculations assume that channels available for activation at the beginning of depolarization equally enter slow and fast recovery pathways, with no interconversion. Fraction of slow and fast recovery during each 95-ms recovery interval is calculated based on measured time constants of fast and slow recovery for WT cells at −80 mV (Fig. 7, F–G) and calculated initial fraction of channels in either fast or slow pathways. (B1) Black circles indicate fraction of channels available for activation before depolarization, red indicates channels in fast recovery pathways before depolarization, and blue indicates channels in slow recovery pathways before depolarization. (B2) Fractions of channels in slow recovery pathways (blue) and fast recovery pathways (red) immediately following inactivation (green arrows in A). (B3) Calculated fraction of peak Nav current normalized to P1 amplitude based on channels available for activation before each test pulse to 0 mV. (B4) Time course of recovery from inactivation based on calculated fraction of channels in fast and slow pathways following P1 or P10 and the measured time constants of recovery. (C) Calculations similar to those in B, but assuming that the slow component of recovery from inactivation is absent (most FGF14 KO cells). This yields no appreciable use-dependent diminution in Nav amplitude and identical single exponential time courses of recovery from inactivation following P1 or P10. (D) Calculations as in B and C, but assuming average fast and slow recovery time constants based on the set of FGF14 KO cells that exhibited a slow component of recovery.

Evaluation of the impact of slow and fast recovery from inactivation on use-dependent diminution of peak Nav amplitude. (A) The basic stimulation protocol for calculation of state occupancies, use-dependent peak current diminution, and 1P/10P recovery time course. From a −80 mV holding potential, a 10-Hz train of 20 5-ms steps to 0 mV was used to produce channel activation and inactivation. This corresponds to a 95-ms recovery interval between steps to 0 mV. Red triangles indicate time points before depolarization and green, after full inactivation. For calculations in B–D, fractional inactivation before P1 is assumed to be 0.05, with inactivated states split evenly between fast and slow recovery pathways. (B) Calculations assume that channels available for activation at the beginning of depolarization equally enter slow and fast recovery pathways, with no interconversion. Fraction of slow and fast recovery during each 95-ms recovery interval is calculated based on measured time constants of fast and slow recovery for WT cells at −80 mV (Fig. 7, F–G) and calculated initial fraction of channels in either fast or slow pathways. (B1) Black circles indicate fraction of channels available for activation before depolarization, red indicates channels in fast recovery pathways before depolarization, and blue indicates channels in slow recovery pathways before depolarization. (B2) Fractions of channels in slow recovery pathways (blue) and fast recovery pathways (red) immediately following inactivation (green arrows in A). (B3) Calculated fraction of peak Nav current normalized to P1 amplitude based on channels available for activation before each test pulse to 0 mV. (B4) Time course of recovery from inactivation based on calculated fraction of channels in fast and slow pathways following P1 or P10 and the measured time constants of recovery. (C) Calculations similar to those in B, but assuming that the slow component of recovery from inactivation is absent (most FGF14 KO cells). This yields no appreciable use-dependent diminution in Nav amplitude and identical single exponential time courses of recovery from inactivation following P1 or P10. (D) Calculations as in B and C, but assuming average fast and slow recovery time constants based on the set of FGF14 KO cells that exhibited a slow component of recovery.

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