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. 2022 Sep 14;20:143. doi: 10.1186/s12964-022-00947-8

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Phosphodiesterases and phosphatases control the baseline PKA activity at the RyR2 and SERCA2 nanodomains in AVMs. Rat AVMs expressing FKBP-AKAR3 and SR-AKAR3 were treated with drugs as indicated. A and B Time courses show the changes in YFP/CFP ratio before and after addition of inhibitor of PDE2 erythro-9-(2-Hydroxy-3-nonyl) adenine hydrochloride (EHNA 10 µmol/L), PDE3 (cilostamide, Clio, 1 µmol/L), PDE4 (rolipram, Roli, 10 µmol/L), or both Cilo and Roli. The maximal increases in YFP/CFP ratio before and after drug treatment were plotted. C and D Time courses show the changes in YFP/CFP ratio before and after addition of phosphatase inhibitor (1 nmol/L and 100 nmol/L, okadaic acid, OA) as indicated. The maximal increases in YFP/CFP ratio of FKBP-AKAR3 and SR-AKAR3 in AVMs after drug treatment were plotted. E and F co-treated with ISO (10 nmol/L) together with phosphatase inhibitor OA (100 nmol/L) as indicated. Time courses show the changes in YFP/CFP ratio before and after addition of drugs. The maximal increases in YFP/CFP ratio of FKBP-AKAR3 and SR-AKAR3 in AVMs before and after stimulation were plotted. Dot plots represent mean ± SEM of indicated number of AVMs from mice. p values were obtained by Student t-test between two groups or by one-way ANOVA analysis followed with Tukey’s multiple comparison test