Fig. 3: Whole-cell currents produced by KCNQ4 mutants. | Experimental & Molecular Medicine

Fig. 3: Whole-cell currents produced by KCNQ4 mutants.

From: Rare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment

Fig. 3

a Representative whole-cell current traces recorded in CHO cells transfected with wild-type (WT) and mutant KCNQ4 with step pulses from −80 mV to 40 mV in 20 mV steps. b Mean current-voltage (I–V) relation curves obtained from steady-state currents elicited at each step pulse voltage. c Summary bar graph of steady-state currents elicited at 40 mV normalized to membrane area (capacitance), obtained from whole-cell current recordings as presented in A. Averaged whole-cell current densities were 151.9 ± 11.6 pA/pF (n = 30), 61.5 ± 8.8 pA/pF (n = 19), 68.6 ± 7.8 pA/pF (n = 17), 81.8 ± 16.4 pA/pF (n = 12), 61.6 ± 4.3 pA/pF (n = 15), 82.3 ± 9.5 pA/pF (n = 19), 38.5 ± 5 pA/pF (n = 16), 30.2 ± 3.8 pA/pF (n = 12), 30.4 ± 5.9 pA/pF (n = 8), 142.5 ± 20.5 pA/pF (n = 4), and 32.4 ± 4.2 pA/pF (n = 9) for WT, p.T278A, p.S273A, p.L281M, p.L295P, p.R433W, p.N264S, p.S269F, p.W276S, p.H455Q and green fluorescent protein only, respectively. Data represent the mean ± SEM. ***P < 0.001 compared to WT. Statistical analysis was performed using one-way ANOVA with Bonferroni’s multiple comparison. d Dominant-negative effects of mutants on KCNQ4-mediated currents were analyzed with a 1:1 ratio of WT and mutants KCNQ4 and step pulses from −80 mV to 40 mV in 20 mV steps. The mean I–V relation curve obtained from the steady-state current values elicited at each step pulse voltage is shown. e Summary bar graph of the steady-state currents elicited at 40 mV normalized to capacitance. The averaged whole-cell current densities were 143.6 ± 24.5 pA/pF (n = 7), 56.6 ± 4.5 pA/pF (n = 11), 69.4 ± 1.1 pA/pF (n = 9), 72 ± 16.4 pA/pF (n = 12), 66.1 ± 6.7 pA/pF (n = 10), 72.9 ± 15.9 pA/pF (n = 10), 46.7 ± 3.4 pA/pF (n = 9), 40.6 ± 6.04 pA/pF (n = 9), 58.8 ± 4.2 pA/pF (n = 10), and 129.2 ± 32.5 pA/pF (n = 4) for WT, p.T278A, p.S273A, p.R433W p.L281M, p.L295P, p.N264S, p.S269F, p.W276S, and p.H455Q, respectively. The red line is the predicted current density if there is no dominant-negative effect. Data represent the mean ± SEM. **P < 0.01, ***P < 0.001 compared to the WT. Statistical analysis was performed using one-way ANOVA with Bonferroni’s multiple comparison

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