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Fig. 6 | Molecular Autism

Fig. 6

From: Biophysical classification of a CACNA1D de novo mutation as a high-risk mutation for a severe neurodevelopmental disorder

Fig. 6

Mutation S652W induces gating changes compatible with a loss-of-function phenotype. a Current-voltage relationship (ICa; mean ± SEM) of WTL vs S652WL recorded in parallel on the same day as described in Fig. 1. Inset: Representative ICa traces of WTL and S652WL upon depolarization to the Vmax. b Normalized steady-state activation and inactivation curves of WTL vs S652WL. Data are presented as mean ± SEM; for parameters and statistics see Table 4. c Window currents of WTL vs S652WL were calculated as in Fig. 1e, f. Data are presented as means for the indicated number of experiments. d Inactivation kinetics of WTL vs. S652WL during a 5-s depolarization to Vmax with Ca2+ as a charge carrier showing no difference in inactivation kinetics between WTL and S652WL. Inset shows the first 2000 ms. Data are presented as mean ± SEM; for statistics and number of experiments, see Table 5. The significant shift of activation and inactivation half-maximal voltage to positive voltages and the absence of a change in inactivation time course was independently confirmed in an independent set of experiments using HEK-293 cells stably expressing β3 and α2δ-1 subunits with essentially identical results. Statistics: one-way ANOVA followed by Bonferroni post hoc test, *p < 0.05. Data are represented as mean ± SEM for the n-numbers indicated. Data were collected from > 3 independent transfections

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