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. 2017 Jul 31;7:6933. doi: 10.1038/s41598-017-07292-8

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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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UBP684 potentiates GluN1/GluN2A receptor responses and slows their deactivation kinetics. (A) UBP684 structure and PAM activity on GluN1/GluN2A receptors expressed in Xenopus oocytes. After obtaining a stable steady-state response to 10 µM L-glutamate and 10 µM glycine, application of 50 µM UBP684 potentiates the agonist response (upper panel). Dose-response of UBP684 potentiation of GluN1/GluN2A receptor responses under saturating agonist conditions (300µM L-glutamate/300 µM glycine) is shown in the lower panel. (B) Whole-cell recordings (left panel) were obtained from HEK293 cells either in dialyzed (top row) or perforated mode (bottom row). Individual cell peak current and deactivation time in response to UBP684 application (right two panels). Using the fast concentration-jump technique, cells were exposed to a solution containing no drug and switched to a solution containing glutamate and glycine (black traces) or glutamate, glycine and UBP694 (red traces). UBP684 (100 µM) potentiated glutamate (100 µM) and glycine (100 µM) induced peak currents in the perforated condition, but not in the dialyzed condition. Slowing of the deactivation rate by UBP684 was observed under both modes. N = 6, *P < 0.05, paired t-test.