Figure 8.
Blocking SERCA reproduced the attenuated intrinsic excitability of STIM1-deleted PNs. A, CPA treatment during the attached recording. CPA (30 μm) decreases firing rates of wild-type PNs to the level of STIM1PKO PNs, while PNs of STIM1PKO seem unaffected by CPA (wild-type, n = 11; STIM1PKO, n = 9). Reduced firing frequency of wild-type PNs was significantly larger than that of STIM1PKO PNs (p = 0.001, inset). Comparing initial firing rates to 30 min after CPA treatment, the initial firing rates of wild-type PNs are remarkably higher than others. B, Somatic SERCAs are important for the regulation of spontaneous firing rates. Local puffing of CPA (600 μm, 4 psi) onto the soma (n = 4, circle, blue) caused a reduction of firing rates, but there was no change in local CPA puffing onto dendrites of wild-type PNs (n = 4, square, blue) and the soma of STIM1PKO PNs (n = 4, triangle, red). After 10 min of treatment, the wild-type soma treatment group only showed significant reduction of firing rates (F = 5.556, p = 0.027). C, 30 min of CPA (30 μm) preincubation reduces the evoked firing rate of wild-type littermates. Wild-type littermates showed significantly higher evoked firing frequency than other groups (wild-type, n = 60; STIM1PKO, n = 43; wild-type + CPA, n = 17; STIM1PKO + CPA, n = 13). At the 600 pA point, the differences between wild-type mice and others are obvious. D, mAHP after preincubation of CPA. Only wild-type littermates were affected by the drug, and mAHP of wild-type littermates became same as other groups. The representative bar graph at 600 pA of current injection shows that wild-type mice had considerably smaller mAHP than other groups. E, CPA strengthened the SFA of wild-type PNs. The instantaneous firing frequency at the 30th spike was significantly lower in the other three groups than wild-type littermates. Data from drug-untreated wild-type and STIM1PKO mice, except A and B, were pooled from Figure 5. One-way ANOVA was used for B, and other details of data and statistics see also Table 2. Error bars denote the SEM. *p < 0.05; **p < 0.01; ***p < 0.001.