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. 2023 Nov 7;33(4):355–373. doi: 10.1093/hmg/ddad188

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© The Author(s) 2023. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Modulation of constitutively active GluD1 and GluD2 M3 variants by d-serine. Representative concentration-response curves showing d-serine modulation of the constitutive current observed for (A) GluD1-A650T and (B) GluD2-A654T. The differences between the baseline current and the current in NMDG⁺ are used to establish theoretical maximum inhibition for each recording. The dotted line represents zero current. (C–F) D-Serine concentration-response curve for d-serine modulation of constitutively active M3 variants GluD1-A650T (C), GluD2-A654D (D), GluD2-L656V (E) and GluD2-T649A. For each experiment, same day control curves recorded for the lurcher variant GluD2-A654T are shown. Unlike GluD2-A654T, GluD2-L656V, GluD2-T649A, we observed that GluD1-A650T is modestly potentiated by d-serine rather than inhibited. A654D shows a near complete loss of d-serine potency.