Fig. 3: AKAP5/AC5 mediate I_Ba potentiation and vasoconstriction upon glucose/NF546.

Representative a diameter recordings, b summary percentage myogenic tone, and c change in myogenic tone from wild-type (WT; n = 9 arteries/5 mice) and AKAP5^−/− (n = 7 arteries/6 mice) cerebral arteries in 10 and 20 mM D-glucose (D-glu). *P < 0.05 with two-tailed Wilcoxon test for b (P = 0.0039 for WT 10 mM D-glu-20 mM D-glu) and two-tailed Mann–Whitney test for c (P = 0.0012 for WT-AKAP5^−/−). d Averaged ICUE3-PM traces (mean = solid line; SEM = shade) and e maximum FRET ratio for WT and AC5^−/− arterial myocytes upon 500 nM NF546 (n = 23 cells/6 WT mice; n = 18 cells/5 AC5^−/− mice), 20 mM D-glu + 500 nM NF546 (n = 22 cells/6 WT mice; n = 15 cells/5 AC5^−/− mice) and after 1 µM forskolin. *P < 0.05 with two-tailed Mann–Whitney test. Single asterisks highlight significant differences between datasets in the absence of forskolin. Double asterisks indicate statistical differences within the same experimental group before and after forskolin. All significant P values are <0.0001. f Exemplary I_Ba traces and g amalgamated current density from WT (n = 7 cells/5 mice), AKAP5^−/− (n = 7 cells/5 mice) and AC5^−/− (n = 7 cells/3 mice) cerebral arterial myocytes before and after 500 nM NF546. *P < 0.05 with two-tailed Wilcoxon test. P = 0.0156 for WT 10 mM D-glu-NF546. h Representative diameter recordings, i summary percentage myogenic tone, and j change in myogenic tone from WT (n = 6 arteries/4 mice), AKAP5^−/− (n = 8 arteries/6 mice), and AC5^−/− (n = 6 arteries/4 mice) cerebral arteries exposed to 500 nM NF546. Scales = 10 μm (vertical) and 5 min (horizontal). *P < 0.05 with two-tailed Wilcoxon test for Dii (P = 0.0313 for WT 10 mM D-glu-NF546) and Kruskal–Wallis one-way ANOVA with Dunn’s multiple for Diii (P = 0.0036 for WT-AKAP5^−/− and P = 0.0040 for WT-AC5^−/−). Initial diameters shown on the traces left side. Data represent mean ± SEM. Source data are provided as Source data file.