Mutants at residue 1784 in Nav1.5 alter the rates and voltage dependence of fast inactivation. (A) Average voltage dependence of fast inactivation in residue 1784 mutants at extracellular pH 7.4. The voltage dependence of fast inactivation was determined by measuring current remaining during a test pulse to −10 mV (b) following conditioning pulses to voltages between −150 and −10 mV (a). Inset: Average midpoints of the steady-state fast inactivation (SSFI) voltage dependence for residue 1784 mutants at pH 7.4 and pH 6.0 (n = 5–9; Table S2). (B) Average time course of fast inactivation recovery at −90 mV in residue 1784 mutants at extracellular pH 7.4 (n = 3–5; Table S3). Rates of recovery from fast inactivation were determined by measuring current during a test pulse (c) following recovery pulses of varying lengths (b) after an initial depolarizing pulse (a). (C) Average time course of fast inactivation onset at −50 mV in residue 1784 mutants at extracellular pH 7.4 (n = 3–5; Table S4). The rates of closed-state fast inactivation onset were determined by measuring the current remaining in a test pulse (b) following conditioning pulses of varying durations (a). (D) Average time constants of fast inactivation (FI) recovery and closed-state onset plotted versus voltage for residue 1784 mutants at extracellular pH 7.4 (n = 3–5; Tables S3 and Table S4). (E) Average time constants of open-state fast inactivation onset plotted versus voltage for residue 1784 mutants at extracellular pH 7.4 (n = 4–9; Table S5). Error bars are SEM.