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. 2017 Dec 15;7:17656. doi: 10.1038/s41598-017-18024-3

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© The Author(s) 2017

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Extracellular cGMP increases membrane expression of GluA1 subunit through activation of the cAMP-PKA-I1-PP1-CaMKII pathway. (A) Extracellular cGMP was added to cerebellar slices in the absence or the presence of an inhibitor of CaMKII (KN62, 10 µM) and membrane expression of GluA1 was analyzed. (B) cAMP levels in cerebellar slices after administration of 40 nM cGMP or 75 µM strychnine. (C–F) Extracellular cGMP was added to cerebellar slices in the absence or the presence of an inhibitor of PKA (1 µM 14–22 Amide) and membrane expression of GluA1 (C) and its phosphorylation at Ser831 (D), at Ser845 (E) and phosphorylation of CaMKKI at Thr286 (F) were analyzed. (G,H) Content of protein phosphatase inhibitor-1 (I1) phosphorylated at Thr 35 (G) and PP1 (H) after treatment with extracellular cGMP. Non-parametric Kruskal-Wallis test (in A,C–F), one-way analysis of variance (in B) and the unpaired Student’s t-test (in G,H) were performed. Values are expressed as percentage of basal and are the mean ± SEM of 10–15 rats. Values significantly different from basal are indicated by asterisk *p < 0.05, **p < 0.01. Values significantly different from cGMP treatment are indicated by a p < 0.05.