FIGURE 2.

Cinacalcet shifted the voltage-dependence of fast inactivation. (A) Representative traces from a protocol used to isolate and evaluate the voltage-dependence of fast inactivation. Measurements were taken by applying a 100 ms depolarization to varying voltages (−140 to +20 mV in 10 mV increments) from a holding potential of −80 mV, and delivering a test pulse to −20 mV in control conditions (black), following inhibition of half of the starting current by 5 µM cinacalcet (blue), and following full inhibition (red). (B) Plot of average normalized peak VGSC currents elicited by test pulse following 100 ms conditioning pulse in control (black; n = 8), following inhibition of half of the starting current by cinacalcet (blue; n = 8), and following full inhibition (red; n = 8) fit to the Boltzmann equation. The 50% inhibition data were collected once cinacalcet had decreased the VGSC current elicited by the step from −80 mV to −20 mV, to 50% of control. Dashed red line indicates average cinacalcet fit normalized to the average control maximum. (C) Plot of individual (black, open circles) and mean (red, filled circles) apparent valence values. 1-W ANOVA RM test returned p < 0.0001 overall, with p = 0.0078 and < 0.0001 for control vs. 50% or control vs. full block respectively by Holm-Sidak corrected multiple comparisons. (D) Plot of individual (black, open circles) and mean (red, filled circles) V_0.5 values. 1-W ANOVA RM test returned p < 0.0001 overall, with p = 0.003 and < 0.0001 for control vs. 50% or control vs. full block respectively by Holm-Sidak corrected multiple comparisons.