Extended Data Fig. 9: The effects of K+ on astrocyte glycolysis and lactate release are dependent on adenosine A2B receptor-mediated signalling.
From: Adenosine signalling to astrocytes coordinates brain metabolism and function
(a) Representative trace and (c) summary data illustrating changes in cytosolic NADH-NAD+ redox state in response to increases in extracellular [K+] (from 3 mM to 15 mM) in cultured astrocytes, recorded in the absence and presence of A2 receptor antagonist ZM241385 (10 µM). To estimate the cytosolic level of glycolysis-derived NADH:NAD+, the cells were treated with an inhibitor of glycolysis iodoacetate (1 mM) at the end of each experiment; (b) Traces illustrating changes in cytosolic NADH-NAD+ redox state in response to 15 mM extracellular [K+] in Adora2bflox/flox astrocytes transduced to express eGFP (control) and in astrocytes of Adora2bflox/flox mice transduced to express iCre recombinase (A2BR-Astro-KD). In panels (a) and (b), traces illustrate averaged (mean ± s.e.m.) recordings from several individual cells in a representative experiment. In panel (c), numbers in parentheses indicate the number of individual cells/number of separate cultures, prepared from the same number of animals. P values, one-way ANOVA followed by Sidak’s post hoc test; (d) Averaged (means ± s.e.m.) traces and summary data illustrating facilitated release of lactate in response to 10 mM extracellular [K+] recorded using lactate biosensors in acute hippocampal slices of mice in the absence and presence of A2 receptor antagonist ZM241385 (10 µM). P value, two-tailed Mann-Whitney test. In panel (d), numbers in parentheses indicate the number of independent slice experiments/number of animals per experimental group. In the box-and-whisker plots, the central dot indicates the mean, the central line indicates the median, the box limits indicate the upper and lower quartiles, and the whiskers extend to 1.5 IQR from the quartiles.
