Journal: Journal of Neurophysiology

Article Title: Mechanisms of severe acute intermittent hypoxia-induced phrenic long-term facilitation

doi: 10.1152/jn.00691.2020

Figure Lengend Snippet: pLTF is abolished following ESI-05 and PI828 treatment. A–D: representative traces of compressed, integrated phrenic nerve activity before and after sAIH following pretreatment with vehicle (A), ESI-05 (EPAC inhibitor, B), PI828 (PI3K/Akt inhibitor, C), and KT-5720 (PKA inhibitor, D). The dashed line in each trace represents baseline. E: phrenic burst amplitude (percent change from baseline) in vehicle (open diamonds)-, PKA inhibitor (filled squares)-, EPAC inhibitor (filled triangles)-, and PI3K/Akt inhibitor (filled circles)-treated rats after AIH, and time control (without AIH, gray diamonds)-treated rats. pLTF is significant in vehicle-treated rats versus EPACi-treated rats at 30-, 60-, and 90-min posthypoxia ($), and at all time-points post-AIH versus time control-treated rats (*), baseline (+), PKAi (#), and PI3K/Akti (&) (all P < 0.05). PKAi-treated rats showed significant pLTF versus baseline at 30-, 60-, and 90-min posthypoxia, and time control-treated rats at 90-min posthypoxia (all P < 0.05). F: frequency (change from baseline; bursts/min) in vehicle-, PKA inhibitor-, EPAC inhibitor-, and PI3K/Akt inhibitor-treated rats after AIH, and time control-treated rats. Small frequency LTF in vehicle-treated rats is observed at 30- and 60-min post-AIH versus baseline (+) (P < 0.05). PI3K/Akti-treated rats had decreased frequency LTF compared with baseline (+) at 15-min post-AIH (P < 0.05). A two-way ANOVA with repeated measures design was utilized, followed by a Tukey post hoc test. Values are means ± SE. AIH, acute intermittent hypoxia; EPAC, exchange protein activated by cyclic AMP; LTF, long-term facilitation; PI3K/Akt, phosphatidylinositol 3-kinase/Akt; pLTF, phrenic long-term facilitation; sAIH, severe AIH. The n for each group is as follows: vehicle 1, n = 10; ESI-05, n = 5; PI828, n = 5; KT-5720, n = 8; time control, n = 10.

Article Snippet: With statistically significant ANOVAs, individual comparisons were made using Tukey post hoc test (SigmaPlot v. 14.0; Systat Software Inc., San Jose, CA).

Techniques: Activity Assay, Control

Journal: Journal of Neurophysiology

Article Title: Mechanisms of severe acute intermittent hypoxia-induced phrenic long-term facilitation

doi: 10.1152/jn.00691.2020

Figure Lengend Snippet: pLTF is abolished following UO126, but marginally constrained by apocynin treatment. A–C: representative traces of compressed, integrated phrenic nerve activity before and after sAIH following pretreatment with vehicle (A), UO126 (MEK/ERK inhibitor, B), and apocynin (NADPH oxidase or NOX inhibitor, C). The dashed line in each trace represents baseline. D: phrenic burst amplitude (percent change from baseline) in vehicle (open diamonds)-, NOX inhibitor (filled squares)-, and MEK/ERK inhibitor (filled triangles)-treated rats after AIH, and time control (without AIH, gray diamonds)-treated rats. pLTF is significant in vehicle-treated rats at all time-points post-AIH versus time control-treated rats (*) and baseline (+), and versus MEK/ERKi-treated rats at 60- and 90-min posthypoxia ($) (all P < 0.05). NOXi-treated rats showed significant pLTF versus baseline, time control-treated rats, and MEK/ERKi-treated rats at all time-points post-AIH (all P < 0.05). E: Frequency (change from baseline; bursts/min) in vehicle-, NOX inhibitor-, and MEK/ERK inhibitor-treated rats after AIH, and time control-treated rats. Small frequency LTF in NOXi-treated rats is observed at all time points post-AIH versus MEK/ERKi-treated rats ($), but only at 30- and 90-min post-AIH versus baseline (+) and time control-treated rats (*) (P < 0.05). MEK/ERKi-treated rats had decreased frequency LTF compared with time control-treated rats (*) and baseline (+) at 15-min post-AIH and compared with vehicle-treated rats at 15- and 30-min post-AIH (#) (all P < 0.05). A two-way ANOVA with repeated measures design followed by a Tukey post hoc test was utilized. Values are means ± SE. AIH, acute intermittent hypoxia; LTF, long-term facilitation; PI3K/Akt, phosphatidylinositol 3-kinase/Akt; pLTF, phrenic long-term facilitation; sAIH, severe AIH. The n for each group is as follows: vehicle 2, n = 10; UO126, n = 5; apocynin, n = 5; time control, n = 7.

Article Snippet: With statistically significant ANOVAs, individual comparisons were made using Tukey post hoc test (SigmaPlot v. 14.0; Systat Software Inc., San Jose, CA).

Techniques: Activity Assay, Control

Journal: Journal of Neurophysiology

Article Title: Mechanisms of severe acute intermittent hypoxia-induced phrenic long-term facilitation

doi: 10.1152/jn.00691.2020

Figure Lengend Snippet: Direct comparison of the change in burst amplitude (percent baseline) and burst frequency (bursts/min) of the phrenic nerve following sAIH at 90-min posthypoxia. A and B: change in phrenic burst amplitude (A) or burst frequency (B) following pretreatment with vehicle, EPAC inhibitor (EPACi), PI3K/Akt inhibitor (PI3K/Akti), PKA inhibitor (PKAi), MEK/ERK inhibitor (MEK/ERKi), NADPH oxidase inhibitor (NOXi), or rats treated as time controls. A: phrenic amplitude after AIH at 90-min posthypoxia is significantly higher in vehicle-treated rats and NOXi rats compared with all other groups B: phrenic burst frequency after AIH at 90-min posthypoxia is significantly higher in NOXi rats compared time control-treated rats, PKAi-treated rats, MEK/ERKi-treated rats, and PI3K/Akti-treated rats. * vs. time control-treated rats, < vs. PKAi-treated rats, # vs. vehicle-treated rats, @ vs. MEK/ERKi-treated rats, $ vs. EPACi-treated rats, and & vs. PI3K/Akti-treated rats; all P < 0.05. A one-way ANOVA followed by a Tukey post hoc test was utilized; values are means ± SE. AIH, acute intermittent hypoxia; EPAC, exchange protein activated by cyclic AMP; PI3K/Akt, phosphatidylinositol 3-kinase/Akt; sAIH, severe AIH; TC, time control.

Article Snippet: With statistically significant ANOVAs, individual comparisons were made using Tukey post hoc test (SigmaPlot v. 14.0; Systat Software Inc., San Jose, CA).

Techniques: Comparison, Control

Journal: Journal of Neurophysiology

Article Title: Mechanisms of severe acute intermittent hypoxia-induced phrenic long-term facilitation

doi: 10.1152/jn.00691.2020

Figure Lengend Snippet: Short-term hypoxic phrenic response. A and B: progressive augmentation of the short-term hypoxic phrenic response was observed in all sAIH-treated rats including vehicle-, EPAC inhibitor (EPACi)-, PI3K/Akt inhibitor (PI3K/Akti)-, PKA inhibitor-, MEK/ERK inhibitor (MEK/ERKi)-, and NADPH oxidase inhibitor (NOXi)-treated rats. 1, 2, and 3 represent hypoxic episodes for sAIH-treated rats or normoxic episodes for time control-treated rats. In A and B, the hypoxic response progressively increases with each episode (* indicates significantly different than 1; and + indicated significantly different from 3; both P < 0.05). There were no changes in time control-treated rats, and all treatment groups were significantly different from time control-treated rats (P < 0.05). A two-way ANOVA with repeated measures design followed by a Tukey post hoc test was utilized; values are means ± SE. AIH, acute intermittent hypoxia; EPAC, exchange protein activated by cyclic AMP; PI3K/Akt, phosphatidylinositol 3-kinase/Akt; sAIH, severe AIH; TC, time control.

Article Snippet: With statistically significant ANOVAs, individual comparisons were made using Tukey post hoc test (SigmaPlot v. 14.0; Systat Software Inc., San Jose, CA).

Techniques: Control