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. Author manuscript; available in PMC: 2020 Oct 3.
Published in final edited form as: Cell Rep. 2020 Sep 22;32(12):108169. doi: 10.1016/j.celrep.2020.108169

Figure 1. The RyR2 E4872Q+/− Mutation Decreases Neuronal Excitability and Upregulates A-type K+ Current of CA1 Neurons.

Figure 1.

(A–D) Images of GFP-tagged RyR2 (A and C) and RyR2-WT (GFP-negative; B and D) mouse brain sections.

(E) Traces of action potential (AP) firing.

(F) Current thresholds for AP firing in WT (10 mice, 30 neurons), 5xFAD+/− (10 mice, 30 neurons), 5xFAD+/−/EQ+/− (10 mice, 30 neurons), and EQ+/− (10 mice, 30 neurons) CA1 neurons.

(G) Current injection-triggered AP firing frequency in WT (10 mice, 30 neurons), 5xFAD+/− (10 mice, 30 neurons), 5xFAD+/− /EQ+/− (10 mice, 30 neurons), and EQ+/− (10 mice, 30 neurons) CA1 neurons.

(H) Traces of A-type K+ current (IA) from 3- to 4-month-old WT, 5xFAD+/−, 5xFAD+/−/EQ+/−, and EQ+/− CA1 neurons.

(I) Normalized IA traces.

(J) Steady-state activation curves of IA.

(K) IA amplitude in 3- to 4-month-old WT (10 mice, 30 neurons), 5xFAD+/− (10 mice, 30 neurons), 5xFAD/EQ+/− (10 mice, 30 neurons), and EQ+/− (10 mice, 30 neurons) CA1 neurons.

(L) IA inactivation kinetics (Tau) from the same number of neurons as in (K).

(M) The midpoints of voltage-dependent activation of IA (VA) for WT (10 mice, 30 neurons), 5xFAD+/− (10 mice, 30 neurons), 5xFAD+/−/EQ+/− (10 mice, 30 neurons), and EQ+/− (10 mice, 30 neurons) CA1 neurons.

(N and O) Current threshold for AP firing (N) and current injection-triggered AP firing frequency (O) without or with the Kv4 channel agonist NS5806 (10 μM) in 5xFAD+/− CA1 neurons (7 mice, 14 neurons).

(P and Q) Whole-cell IA (P) and inactivation time constant Tau (Q) in Kv4.2/KChIP4-transfected HEK293 cells expressing RyR2 WT (n = 21) or the RyR2 E4872Q+/− mutation (n = 26).

(R) Biotin-labeled surface Kv4.2 in Kv4.2/KChIP4-transfected HEK293 cells expressing RyR2 WT or the RyR2 E4872Q+/− mutation.

Scale bars, 2 mm in (A) and (B) and 10 μm in (C) and (D). Data shown are the median and range (Kruskal-Wallis test with Dunn-Bonferroni post hoc test, Wilcoxon matched-pairs signed rank test, and Mann-Whitney U test; *p < 0.5, **p < 0.01 versus WT, ##p < 0.01; 5xFAD+/−/EQ+/− versus 5xFAD+/−; NS, not significant). See also Figure S1.

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