Extended Data Fig. 8: Related to Fig. 3: action potential characteristics of Purkinje cells from Hpdl+/+, Hpdl+/−, Hpdl−/− and 4-HMA-treated Hpdl−/− mice.
From: Coenzyme Q headgroup intermediates can ameliorate a mitochondrial encephalopathy
a, Action potential characteristics of Purkinje cells from P8-10 Hpdl+/+, Hpdl+/−, Hpdl−/− and 4-HMA-treated Hpdl−/− pups. An average action potential is shown in panel A and the phase plane diagram is shown in panel B. Significant action potential shape differences can be seen between Purkinje cells from Hpdl+/+ and 4-HMA-treated Hpdl−/− pups. Purkinje cells from 4-HMA-treated Hpdl−/− pups had a significantly lower spike threshold than the Hpdl+/+ (p = 0.0076) and Hpdl−/− pups (p = 0.0207; panel C). The spike threshold for Purkinje cells from the Hpdl+/− and 4-HMA-treated Hpdl−/− pups trended to difference but was not significant (p = 0.0506), consistent with 4-HMA treatment rescuing Hpdl−/− pup grip strength to the level of Hpdl+/− mice (Fig. 3g). The spike half-width of Purkinje cells from the 4-HMA-treated Hpdl−/− pups was significantly narrower than all three treatments (Hpdl+/+: p < 0.0001; Hpdl+/−: p = 0.0002; Hpdl−/−: p < 0.0001; panel E). Finally, Purkinje cells from 4-HMA-treated Hpdl−/− pups had a shallower action half-potential (AHP) amplitude compared to Hpdl+/+and Hpdl−/− pups (WT: p = 0.0008; KO: p = 0.0461; panel F). The 4-HMA-treated Hpdl−/− pup statistics resemble those of Hpdl+/+ pups in the P17-19 group (Extended Data Fig. 8b). b, Action potential characteristics of P17-19 Hpdl+/+, Hpdl+/−, and 4-HMA-treated Hpdl−/− pups. An average action potential is shown in panel A and the phase plane diagram is shown in panel B. The spike threshold, spike amplitude, and spike half-width are comparable in all three groups. The AHP for Purkinje cells from 4-HMA-treated Hpdl−/− pups was lower than for Hpdl+/+pups (p = 0.0268). c, Peak frequency and action potential characteristics of Purkinje cells from P56-57 Hpdl+/+, Hpdl+/−, and 4-HMA-treated Hpdl−/− mice. The peak frequency, spike amplitude, spike half-width, spike threshold, and AHP amplitude are comparable in all three groups. All electrophysiological data are presented as the averages of at least 10 Purkinje cells (Supplementary Table 4). Significance was tested by two-way ANOVA followed by Dunnett’s multiple comparison test.
