Fig. 3: SK channel inhibition in WT neurons recapitulates the 3xTg phenotype.
a Representative traces of the tail current in response to a 100 ms depolarization step to –17 mV from Vhold (–72 mV) in the whole-cell configuration. b Reduced tail current maximal amplitude (cells/mice, WT: 3 mo 66/7, 6 mo 25/7, 12 mo 20/6, 18 mo 37/6; 3xTg: 3 mo 42/3, 6 mo 40/8, 12 mo 42/7, 18 mo 28/6; two-way ANOVA Fgenotype = 8.743, P = 0.0034; Fage = 10.57, P < 0.0001) and (c) area under the curve (AUC, Fgenotype = 13.79, P = 0.0002, Fage = 10.03, P < 0.0001) in 3xTg DA neurons. d Perforated-patch recordings from spontaneously firing WT cells at baseline (black) and in the presence of apamin (1−3 nM; orange). e Increased firing frequency (n = 8 neurons, 6 mice; two-tailed Wilcoxon, P = 0.0078, W = 36.00) and f CVISI (two-tailed Wilcoxon, P = 0.0078, W = 36.00) in presence of apamin. g Depolarized apparent spike threshold in response to apamin (paired two-tailed t-test, P = 0.0050, t = 4.031). h ISI voltage trajectory averages. The effect of apamin is reminiscent of the trajectories from 3xTg neurons (panel 2k). i Depolarized mAHP (paired two-tailed t-test, P = 0.0022, t = 4.722) and (j) absolute minimum ISI voltages (paired two-tailed t-test, P = 0.0018, t = 4.853) in apamin. Error bars represent standard error. Source data are provided as a Source Data file.
