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. 2023 Aug 22;120(35):e2306479120. doi: 10.1073/pnas.2306479120

Fig. 5.

Fig. 5.

Chronic PI3K inhibition restores Kir2.1 currents, K+-induced dilation, functional hyperemia, and memory deficits in 12-M-old Col4a1+/G394V mice. (A) Illustration showing GSK1059615 treatment plan. (B) Representative I-V traces and summary data showing Kir2.1 current densities in freshly isolated capillary ECs from 12-M-old Col4a1+/+ and Col4a1+/G394V mice treated with vehicle (saline) or GSK1059615 (10 mg/kg) for 28 d, s.c. (n = 5 to 8 cells from 3 to 4 animals per group, *P < 0.05, ns = not significant, nonrepeated measures two-way ANOVA). (C and D) Representative traces (C) and summary data (D) showing K+ (10 mM, blue box)-induced dilation of upstream arterioles in preparations from 12-M-old Col4a1+/+ and Col4a1+/G394V mice treated with vehicle (saline) or GSK1059615 (10 mg/kg) for 28 d, s.c. (n = 6 to 7 preparations from three animals per group, *P < 0.05, ns = not significant, nonrepeated measures two-way ANOVA). (E and F) Representative traces (E) and summary data (F) showing the increase in blood flow following 1-s contralateral whisker stimulation (WS) in 12-M-old Col4a1+/+ and Col4a1+/G394V mice treated with vehicle (saline) or GSK1059615 (10 mg/kg) for 28 d, s.c. (n = 5 animals per group, *P < 0.05, ns = not significant, nonrepeated measures two-way ANOVA). (G–J) Latency (G), duration (H), rise rate (I), and decay rate (J) were also analyzed (n = 5 animals per group, *P < 0.05, ns = not significant, nonrepeated measures two-way ANOVA). (K) Summary data showing alternation index, an indicator spatial working memory, of 12-M-old Col4a1+/+ and Col4a1+/G394V mice before and after treatment with vehicle (saline) or GSK1059615 (10 mg/kg) for 28 d, s.c. (n = 8 to 9 animals per group, *P < 0.05, ns = not significant, repeated measures two-way ANOVA). (L and M) Summary data showing max alternation (L) and distance moved (M), indicative of exploratory activity, in 12-M-old Col4a1+/+ and Col4a1+/G394V mice before and after treatment with vehicle (saline) or GSK1059615 (10 mg/kg) for 28 d, s.c. (n = 8 to 9 animals per group, *P < 0.05, ns = not significant, repeated measures two-way ANOVA).