Figure 7. RyR-mediated SR Ca²⁺ leak contributes to respiratory dysfunction and reduces voluntary activity in a murine model of HD.

(A–D) Representative records of diaphragmatic specific force production measured ex vivo at 20 and 120 Hz in muscle bundles under isometric conditions in WT, Q175, Q175+ARM036, and Q175+S107 mice. (E) Average force-frequency relationship recorded in WT (n = 13), Q175 (n = 10), Q175+ARM036 (n = 9), and Q175+S107 (n = 8) mice. Data (mean ± SEM) analysis was performed by 2-way ANOVA. Bonferroni’s posttest revealed *P < 0.05 vs. WT, ^#P < 0.05 Q175 vs. Q175+S107/ARM036. (F) Tidal volume (mL/g) at rest and during CO₂ stimulation. (G) Respiratory frequency (bpm) at rest and during CO₂ stimulation (H) Minute volume (mL/g) at rest and during CO₂ stimulation in WT (n = 15), Q175 (n = 19), Q175+ARM036 (n = 10), and Q175+S107 (n = 10). The CO₂ values were recorded 10 minutes after the initiation of CO₂ stimulation. Data (mean ± SD) analysis was performed by 1-way ANOVA. Bonferroni’s posttest revealed *P < 0.05 vs. WT, ^#P < 0.05 vs. Q175. (I–K) Active time (seconds), mean speed (m/min), and running distance (m) for voluntary activity on running wheels, respectively, in WT (n = 13), Q175 (n = 10), Q175+ARM036 (n = 10), and Q175+S107 mice (n = 12). Data (mean ± SD) analysis was performed by 1-way ANOVA. Bonferroni’s posttest revealed *P < 0.05 vs. WT, ^#P < 0.05 vs. Q175.