Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2021 Oct 13;12:5962. doi: 10.1038/s41467-021-26263-2

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2021

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/.

PMC Copyright notice

Fig. 8 — A Traces of respiratory activity from saline (black) or PF-04531083 (gray) treated Tcf4^+/+ and saline (red) or PF-04531083 (orange) treated Tcf4^tr/+ mice during exposure to room air, 100% O₂ and 3–7% CO₂ (balance O₂). B Summary plots of minute ventilation show that PF-04531083 improved CO₂-dependent respiratory output in Tcf4^tr/+ mice (0–7% CO₂ slope: 0.59 ± 0.08 saline vs. 0.79 ± 0.10 PF-04531083; n = 5 biologically independent animals, p = 0.0314, data are presented as mean values ± SEM) to a level not different from Tcf4^+/+ mice (0–7% CO₂ slope: 1.11 ± 0.1; n = 5 biologically independent animals, p > 0.05, data are presented as mean values ± SEM). C Summary plots of minute ventilation show that systemic application of PF-06305591 (2 mg/kg, a selective Nav1.8 channel blocker that does not readily cross the blood brain barrier) minimally effected respiratory activity in both genotypes (0–7% CO₂ slope: 0.56 ± 0.06 saline vs. 0.50 ± 0.09 PF-06305591; n = 5 biologically independent animals/genotype, p > 0.05, data are presented as mean values ± SEM) (Tcf4^tr/+ mice injected with Pf-06305591 are indicated with blue). D Traces of raw and integrated (∫) diaphragm and abdominal EMG activity show that Tcf4^tr/+ mice treated with saline (30 µL; I.P.) show a diminished Dia_EMG response to CO₂ and completely lacked Abd_EMG activity, even at 7% CO₂. Systemic (I.P.) administration of PF-04531083 (40 mg/kg) increased CO₂-dependent Dia_EMG but not Abd_EMG activity in Tcf4^tr/+ mice. E, F Summary data show effects of CO₂ on Dia_EMG amplitude (E n = 6 biologically independent animals/genotype, data are presented as mean values ± SEM) and frequency (F n = 6 biologically independent animals/genotype, data are presented as mean values ± SEM) in Tcf4^tr/+ mice that received saline or PF-04531083. These results are entirely consistent with the respiratory phenotype exhibited by awake Tcf4^tr/+ mice under control conditions and after PF-04531083 treatment (Fig. 7). Asterisk (*) indicate the different between genotypes; #, used to distinguish difference between PF-04531083 injected mice of both genotypes. ^, different from 0% CO₂ within condition (Dia_EMG). One symbol = p < 0.05, two symbols = p < 0.01, three symbols = p < 0.001, four symbols = p < 0.0001 (two-way RM-ANOVA with Tukey’s multiple comparison test).