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. 2022 Jul 15;13:4114. doi: 10.1038/s41467-022-31817-z

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© The Author(s) 2022

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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Fig. 4 — a–c Measurement of [MK-801] dependence of τ_M at pH 7.2. a, b MCI protocol with 1 μM (a) and 10 μM (b) MK-801. A ~20 s V_m step to 30 mV was performed after MK-801 application to allow full recovery from MK-801 inhibition. c Min I_MCI/I_Control with 1 μM (0.459 ± 0.035; n = 4) and 10 μM MK-801 (0.097 ± 0.029; n = 5) compared with two-sided t-test (t = 7.94, df = 7, p = 0.000096; left); τ_M of MCI onset with 1 μM (1002 ± 135 ms, n = 4) and 10 μM MK-801 (311 ± 59 ms, n = 5) compared with two-sided t-test (t = 5.06, df = 7, p = 0.0015; right). d, e Investigation of memantine reblock during recovery from MCI. Memantine was applied using the pH 9.0 jump protocol because of the higher memantine potency observed at elevated pH (Fig. 1). Amiloride was used with cells that exhibited significant proton-activated currents. d Control (no V_m jump) MCI protocol with 100 μM memantine (left), and overlays of I_Control and I_MCI (I_MCI in red; right). e Same as d, except with two 500 ms V_m steps to 50 mV performed during recovery from MCI. Arrows in the overlays in d and e show time of I_MCI/I_Control measurement (time corresponding to 200 ms after the end of the second V_m step). f I_MCI/I_Control measured at the time shown by arrows in the overlays (I_MCI/I_Control: without V_m steps (d), 0.350 ± 0.017, n = 5; with V_m steps (e), 0.375 ± 0.069, n = 5) compared with two-sided t-test (t = 0.344, df = 8, p = 0.74). In c, f, mean ± SEM is plotted.