Fig. 5: SK channel-mediated increase in glycolytic activity is critical for neuroprotection.

a, b Representative of the normalized extracellular acidification rate (ECAR) in HT22 cells following the application of CyPPA (5 and 10 µM). Left panel depicts cells treated in glucose, right panel treated in galactose. b represents area under the curve quantification of the ECAR values presented in panel a, with background subtraction. Data are presented as mean ± SD, n = 3–6 per condition, *p < 0.05, **p < 0.01 ***p < 0.001 compared to control. c Lactate measurement in medium of HT22 cells in glucose after treatment with CyPPA (10, 25, 50 µM) for 0, 2, 4, or 6 h. Data are presented as mean ± SD, n = 3 per condition, *p < 0.05, **p < 0.01, ***p < 0.001 CyPPA treatment versus control for the same timepoint d Lactate release following treatment with CyPPA (10 µM) in the presence or absence of dichloroacetate (DCA, 10 mM) for 6 h in glucose (left panel) or galactose (right panel) in HT22 cells (12.000 cells/well). Data are presented as mean ± SD, n = 3 per condition, **p < 0.01, ***p < 0.001 CyPPA treatment versus control for the same timepoint, ^###p < 0.001 combination DCA + CyPPA treatment versus CyPPA alone for the same timepoint. e, f MTT assay in HT22 cells treated with erastin (1.5 µM, 16 h, glucose (e), galactose (f)) in the presence or absence of CyPPA (10 µM gray bars) and pre-treated for 8 h with DCA (10 mM) and CyPPA. Data are presented as mean ± SD, n = 6, ***p < 0.001, ^###p < 0.001, ^$$$p < 0.001, *compared to control, ^#compared to erastin, ^$compared to erastin ⁺ CyPPA. g MTT assay of HT22 cells pre-treated for 6 h with lactate (150 mM) and challenged with erastin (1 or 1.5 μM) for 16 h. All experiments were independently repeated at least three times.