Figure 10. Diminution of AP-evoked peak... | Rockefeller University Press

$Diminution of AP-evoked peak inward current with different holding potentials and AP frequencies.(A) Peak inward current evoked by each AP clamp waveform applied at 4 Hz was normalized to the maximal available current defined in a given cell using a standard Nav activation protocol (Fig. 1 A) from a holding potential of −80 mV. At −50 mV, the initial AP is reduced in amplitude by ∼50% compared with that from −80 mV and diminishes to <20% by the fifth AP command. The time base corresponds to the total elapsed time of the protocol as shown in Fig. 1 B. Number of cells: −50 mV, n = 4; −60 mV, n = 3; −70 mV, n = 2; −80 mV, n = 1. Error bars here and in other panels are SD. (B) Normalized inward current amplitude at different resting/holding potentials is shown for a 10-Hz AP train. (C) Normalized inward current amplitude is shown for a 20-Hz AP train. (D) Predicted decrements in peak Nav current were calculated as follows. Availability at a given holding potential was determined from the steady-state inactivation curve (Fig. 1 E) with a 250-ms prepulse. Measured fast and slow recovery time constants (Fig. 3 C) were used to calculate fractional recovery during given sojourns at particular voltages. The predicted decrement based on the protocol of Fig. 10 B was calculated for the 4-Hz AP train, assuming that all Nav current inactivates during each AP, with the first AP driving half the channels into a slow recovery pathway and half into a fast recovery pathway. Recovery than occurs following the AP for a period of 36 ms corresponding to an afterhyperpolarization ranging from −56 to −50 mV; for simplicity, we assumed −50 mV for this interval. Then, the additional recovery that occurs during the interval between sweeps at the specified recovery voltages of −50, −60, −70, or −80 mV was calculated. For comparison, the calculated AP decrement when all inactivation is exclusively via a fast recovery pathway is also shown (dotted lines; red dotted line indicates −50 mV). (E) The same calculations as in D were done for a 10-Hz train showing the deeper decrement in AP amplitudes, because of slower recovery intervals. (F) Fractional decrement in AP amplitude calculated for the 20-Hz train is shown. (G) The data from A–C are recast to directly compare 4-, 10-, and 20-Hz trains all for a given holding potential (−50 mV). (H) As in G, but for −60 mV. (I) As in G, but for −70 mV. (J–L) The calculated decrements for the conditions plotted in G–I are shown.$

Figure 10.

Diminution of AP-evoked peak inward current with different holding potentials and AP frequencies. (A) Peak inward current evoked by each AP clamp waveform applied at 4 Hz was normalized to the maximal available current defined in a given cell using a standard Nav activation protocol (Fig. 1 A) from a holding potential of −80 mV. At −50 mV, the initial AP is reduced in amplitude by ∼50% compared with that from −80 mV and diminishes to <20% by the fifth AP command. The time base corresponds to the total elapsed time of the protocol as shown in Fig. 1 B. Number of cells: −50 mV, n = 4; −60 mV, n = 3; −70 mV, n = 2; −80 mV, n = 1. Error bars here and in other panels are SD. (B) Normalized inward current amplitude at different resting/holding potentials is shown for a 10-Hz AP train. (C) Normalized inward current amplitude is shown for a 20-Hz AP train. (D) Predicted decrements in peak Nav current were calculated as follows. Availability at a given holding potential was determined from the steady-state inactivation curve (Fig. 1 E) with a 250-ms prepulse. Measured fast and slow recovery time constants (Fig. 3 C) were used to calculate fractional recovery during given sojourns at particular voltages. The predicted decrement based on the protocol of Fig. 10 B was calculated for the 4-Hz AP train, assuming that all Nav current inactivates during each AP, with the first AP driving half the channels into a slow recovery pathway and half into a fast recovery pathway. Recovery than occurs following the AP for a period of 36 ms corresponding to an afterhyperpolarization ranging from −56 to −50 mV; for simplicity, we assumed −50 mV for this interval. Then, the additional recovery that occurs during the interval between sweeps at the specified recovery voltages of −50, −60, −70, or −80 mV was calculated. For comparison, the calculated AP decrement when all inactivation is exclusively via a fast recovery pathway is also shown (dotted lines; red dotted line indicates −50 mV). (E) The same calculations as in D were done for a 10-Hz train showing the deeper decrement in AP amplitudes, because of slower recovery intervals. (F) Fractional decrement in AP amplitude calculated for the 20-Hz train is shown. (G) The data from A–C are recast to directly compare 4-, 10-, and 20-Hz trains all for a given holding potential (−50 mV). (H) As in G, but for −60 mV. (I) As in G, but for −70 mV. (J–L) The calculated decrements for the conditions plotted in G–I are shown.

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