Endothelin B (ETB) antagonist reduces high-salt diet (HSD)-induced suprachiasmatic nucleus (SCN) hyperexcitability at night. (A) Violin plots of spontaneous action potential frequencies of SCN neurons treated with ETB antagonist (A-192621, 1 µm) or vehicle (DMSO, 0.03%) from normal salt diet- (NSD-) or HSD-fed mice. Blocking ETB significantly reduced neuronal activity in neurons from HSD-fed mice (diet × treatment interaction, H(1) = 9.430, P = .002; HSD-veh vs. HSD-antagonist post hoc, P < .001), but did not affect neurons from NSD-fed controls (P = 1.00). Solid and dotted lines indicate median and quartiles, respectively. n = 153 (NSD-veh), 177 (NSD-antagonist), 176 (HSD-veh), and 172 (HSD-antagonist) cells; 4 mice per group. (B) Representative loose-patch traces (5 s) from each group. Scale bars: 2 s, 50pA. (C) Percentage of silent (empty bars) versus spiking (filled bars) for cells differed between groups (3-way interaction, χ2(1) = 3.965, P = .046), with HSD-veh slices having significantly more spiking cells than all other groups (P < .05).
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