Fig. 3: Ca²⁺ dysregulation in the neurons with inefficient endogenous γ-secretase.

A Baseline γ-secretase activity and calcium levels before and after 100 μM Glu stimulation were measured using the C99 720-670 and YC3.6 sensors in individual neurons, respectively. B The neurons were divided into four groups based on γ-secretase activity (720/670 ratio: below -1 standard deviation (SD), −1SD to Mean, Mean to +1 SD, and over +1 SD), and baseline Ca²⁺ levels were compared among the groups. N = 11–49 neurons. One-way ANOVA, *<0.05, **<0.01 (C) Post 5 min recording baseline Ca²⁺ levels, the neurons were treated with 100 μM Glu. Then, the changes in Ca²⁺ levels were recorded overtime for 15 min and compared among the four groups with different γ-secretase activity. Repeated ANOVA, ****<0.0001. D In Ca²⁺-free medium, Glu-induced Ca²⁺ influx was not detectable. N = 16–57 neurons. E The baseline 720/670 ratio, representing γ-secretase activity, correlates with the magnitude of Ca²⁺ influx (YC3.6. FRET ratio 20 min post-Glu stimulation was divided by that of before stimulation). N = 99 neurons, Y = 0.491X + 1.05, R² = 0.272, Pearson correlation coefficient, ****<0.0001.