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Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator
Previously our computational modeling studies (Phillips et al., 2019) proposed that neuronal persistent sodium current (I(NaP)) and calcium-activated non-selective cation current (I(CAN)) are key biophysical factors that, respectively, generate inspiratory rhythm and burst pattern in the mammalian p...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262387/ https://www.ncbi.nlm.nih.gov/pubmed/35796425 http://dx.doi.org/10.7554/eLife.74762 |
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author | Phillips, Ryan S Koizumi, Hidehiko Molkov, Yaroslav I Rubin, Jonathan E Smith, Jeffrey C |
author_facet | Phillips, Ryan S Koizumi, Hidehiko Molkov, Yaroslav I Rubin, Jonathan E Smith, Jeffrey C |
author_sort | Phillips, Ryan S |
collection | PubMed |
description | Previously our computational modeling studies (Phillips et al., 2019) proposed that neuronal persistent sodium current (I(NaP)) and calcium-activated non-selective cation current (I(CAN)) are key biophysical factors that, respectively, generate inspiratory rhythm and burst pattern in the mammalian preBötzinger complex (preBötC) respiratory oscillator isolated in vitro. Here, we experimentally tested and confirmed three predictions of the model from new simulations concerning the roles of I(NaP) and I(CAN): (1) I(NaP) and I(CAN) blockade have opposite effects on the relationship between network excitability and preBötC rhythmic activity; (2) I(NaP) is essential for preBötC rhythmogenesis; and (3) I(CAN) is essential for generating the amplitude of rhythmic output but not rhythm generation. These predictions were confirmed via optogenetic manipulations of preBötC network excitability during graded I(NaP) or I(CAN) blockade by pharmacological manipulations in slices in vitro containing the rhythmically active preBötC from the medulla oblongata of neonatal mice. Our results support and advance the hypothesis that I(NaP) and I(CAN) mechanistically underlie rhythm and inspiratory burst pattern generation, respectively, in the isolated preBötC. |
format | Online Article Text |
id | pubmed-9262387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-92623872022-07-08 Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator Phillips, Ryan S Koizumi, Hidehiko Molkov, Yaroslav I Rubin, Jonathan E Smith, Jeffrey C eLife Neuroscience Previously our computational modeling studies (Phillips et al., 2019) proposed that neuronal persistent sodium current (I(NaP)) and calcium-activated non-selective cation current (I(CAN)) are key biophysical factors that, respectively, generate inspiratory rhythm and burst pattern in the mammalian preBötzinger complex (preBötC) respiratory oscillator isolated in vitro. Here, we experimentally tested and confirmed three predictions of the model from new simulations concerning the roles of I(NaP) and I(CAN): (1) I(NaP) and I(CAN) blockade have opposite effects on the relationship between network excitability and preBötC rhythmic activity; (2) I(NaP) is essential for preBötC rhythmogenesis; and (3) I(CAN) is essential for generating the amplitude of rhythmic output but not rhythm generation. These predictions were confirmed via optogenetic manipulations of preBötC network excitability during graded I(NaP) or I(CAN) blockade by pharmacological manipulations in slices in vitro containing the rhythmically active preBötC from the medulla oblongata of neonatal mice. Our results support and advance the hypothesis that I(NaP) and I(CAN) mechanistically underlie rhythm and inspiratory burst pattern generation, respectively, in the isolated preBötC. eLife Sciences Publications, Ltd 2022-07-07 /pmc/articles/PMC9262387/ /pubmed/35796425 http://dx.doi.org/10.7554/eLife.74762 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Neuroscience Phillips, Ryan S Koizumi, Hidehiko Molkov, Yaroslav I Rubin, Jonathan E Smith, Jeffrey C Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator |
title | Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator |
title_full | Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator |
title_fullStr | Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator |
title_full_unstemmed | Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator |
title_short | Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator |
title_sort | predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262387/ https://www.ncbi.nlm.nih.gov/pubmed/35796425 http://dx.doi.org/10.7554/eLife.74762 |
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