Suprachiasmatic nucleus (SCN) neuronal response to endothelin-3 (ET-3) is dependent on monocarboxylate transporter (MCT) lactate transporters. (A) Violin plots of spontaneous action potential frequencies of neurons from SCN slices treated with vehicle (DMSO, 0.2%), MCT inhibitor (2-cyano-3-(4-hydroxyphenyl)-2-propenoic acid [CHC], 200 µm), ET-3 (10 n m), or CHC + ET-3. ET-3 significantly increased SCN firing rate, and this was blocked with CHC (CHC × ET-3 interaction, H(1) = 12.70, P < .001). Solid and dotted lines indicate median and quartiles, respectively. n = 135 (veh), 130 (CHC), 134 (ET-3), and 143 (CHC + ET-3) cells; 3 mice per group. ****P < .001 compared to all other groups. (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 treatment groups (3-way interaction, χ2(1) = 3.971, P = .046), with ET-3 slices having significantly more spiking cells than all other groups (P < .05).
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