Fig. 4: Effect of JNJ-67869386 and JNJ-799760 on the kinetics of open-state desensitization. | Communications Biology

Fig. 4: Effect of JNJ-67869386 and JNJ-799760 on the kinetics of open-state desensitization.

From: Molecular mechanism and structural basis of small-molecule modulation of the gating of acid-sensing ion channel 1

Fig. 4

a Current traces (scaled to the control peak) showing pH 5.0-induced desensitization in control, JNJ-67869386 and JNJ-799760 (both 100 nM). Scale bar: 1 s. b Summary of 80–20% current decay time for all experiments like (a). Data for JNJ-67869386 (n = 10) and JNJ-799760 (n = 7) are both statistically different from control (n = 9) (p < 0.001; one-way ANOVA). Data for individual cells are shown in open circles. c and d Current traces showing the time course of recovery from pH 5.0-induced desensitization without (c) and with (d) 100 nM JNJ-67869386. A 14 s pH 5.0 pulse is immediately preceded by a brief pH 6.0 test pulse and followed by a pH 8.2 pulse interspersed with brief pH 6.0 test pulses at various intervals (thin vertical bars above current trace). In some experiments, brief pH 6.0 pulses are replaced with brief pH 5.0 pulses. e Summary of all experiments like (c) and (d). Data are normalized to the first pH 6.0 (solid symbols) or pH 5.0 (open symbols) peak and fitted to a single or double exponential function with time constants of 250.2 ± 17.3 ms (test/desensitizing pH = pH 6.0/5.0 control; n = 9), 369.8 ± 113.8 ms/1.2 ± 0.5 s (pH 6.0/5.0 JNJ-67869386; n = 5), 258.6 ± 36.6 ms (pH 5.0/5.0 control; n = 6) and 358.6 ± 56.2 ms (pH 5.0/5.0 JNJ-67869386; n = 7), respectively. The JNJ-67869386 data for both pH 6.0/5.0 and pH 5.0/5.0 are statistically different from the respective control (p < 0.001; two-way ANOVA).

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