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Fig. 6 | Molecular Autism

Fig. 6

From: Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns

Fig. 6

Neurons lacking FMRP have reduced IBKCa densities and their burst properties are insensitive to paxilline. a Large Ca-activated potassium currents (IBKCa) evoked by a depolarizing voltage ramp from −110 to +40 mV, 10 mV/s, with a hold of 50 ms at +40 mV. b The IBKCa was isolated by subtracting the currents recorded in the absence and presence of paxilline (10 μM). c I–V curves plotted from the ramp-evoked IBKCa showing the decreased IBKCa in neurons lacking FMRP. Currents are normalized to the corresponding cell capacitance. d Quantification of current densities at + 40 mV show significant decrease of IBKCa in neurons lacking FMRP. Overall, the mean current densities are 11.73 ± 1.49 (FMR1+/y, n = 15, N = 3); 7.4 ± 1.43 (CON2, n = 14, N = 3); 3.57 ± 0.62 (FMR1/y, n = 14, N = 3); 1.44 ± 0.78 (FXS3, n = 12, N = 3). *p < 0.05, ***p < 0.001, two-way repeated measures ANOVA with post hoc Tukey’s test, paired t test, Wilcoxon test. e Representative traces illustrating spontaneous bursts recorded from either a FMR1+/y neuron or a FMR1/y neuron before and after the application of paxilline (10 μM) and illustrating the increase of action potential burst frequencies in FMR1+/y neurons in the presence of paxilline. f Quantification of the number of bursts recorded from FMR1+/y, CON2, FMR1/y, or FXS3 neurons before (open symbols) or after (closed symbols) application of paxilline. Overall, the mean number of bursts are 6.7 ± 1.086 (FMR1+/y, n = 10, N = 3); 13.8 ± 1.85 (FMR1+/y + paxilline, n = 10, N = 3); 5.6 ± 1.08 (CON2, n = 10, N = 3); 11.3 ± 1.94 (CON2 + paxilline, n = 10, N = 3); 25.5 ± 4.51 (FMR1/y , n = 10, N = 3); 26 ± 5.12 (FMR1−/y + paxilline, n = 10, N = 3); 25.4 ± 6.6 (FXS3, n = 10, N = 3); 26.5 ± 5.95 (FXS3 + paxilline, n = 10, N = 3). g Quantification of the duration of bursts recorded from FMR1+/y, CON2, FMR1/y, or FXS3 neurons before (open symbols) or after (closed symbols) application of paxilline. Overall, mean burst duration are 40.97 ± 8.68 s (FMR1+/y); 38.47 ± 7.85 s (FMR1+/y + paxilline); 58.65 ± 13.12 s (CON2); 56.08 ± 14.04 s (CON2 + paxilline); 2.65 ± 0.53 s (FMR1/y); 3.08 ± 0.68 s (FMR1−/y + paxilline); 4.107 ± 0.64 s (FXS3); 3.93 ± 0.77 (FXS3 + paxilline). **p < 0.01, ***p < 0.001, paired t test, Wilcoxon test

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