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. 2020 Dec 9;10:21510. doi: 10.1038/s41598-020-78488-8

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© The Author(s) 2020

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 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/.

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Dose-dependent sparing effect of TTA-P2 on isoflurane-induced hypnosis in the mutant and WT mice. (A) Percent isoflurane at LORR for WT mice. Data from WT mice injected with vehicle in Fig. 1B is used here as baseline. WT mice have a dose dependent decrease in the % isoflurane as the dose of TTA-P2 was escalated (one-way ANOVA: F_3,36 = 29.14, p < 0.001). Bonferroni multiple comparison’s test further elucidated significant differences between 15% cyclodextrin and 30 mg/kg TTA-P2 (p < 0.001), 15% cyclodextrin and 60 mg/kg TTA-P2 (p < 0.001), 10 mg/kg TTA-P2 and 30 mg/kg TTA-P2 (p = 0.007), and 10 mg/kg TTA-P2 and 60 mg/kg TTA-P2 (p = 0.001). (B) Percent isoflurane at LORR for Ca_V3.3 KO cohort. Data from mutant mice injected with vehicle in Fig. 1B is used here as control. Mutant mice had a dose dependent decrease in percent isoflurane for LORR as the dose of TTA-P2 increased (one-way ANOVA: F_3,36 = 115.50, p < 0.001). Bonferroni multiple comparison’s test further identified significant differences between 15% cyclodextrin and 10 mg/kg TTA-P2 (p < 0.001), 15% cyclodextrin and 30 mg/kg TTA-P2 (p < 0.001), 15% cyclodextrin and 60 mg/kg TTA-P2 (p < 0.001), 10 mg/kg TTA-P2 and 60 mg/kg TTA-P2 (p < 0.001), 30 mg/kg TTA-P2 and 60 mg/kg TTA-P2 (p = 0.004).