Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy.
GABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increa...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3269439?pdf=render |
| _version_ | 1818900025547161600 |
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| author | Keith B Hengen Nathan R Nelson Kyle M Stang Stephen M Johnson Stephanie M Crader Jyoti J Watters Gordon S Mitchell Mary Behan |
| author_facet | Keith B Hengen Nathan R Nelson Kyle M Stang Stephen M Johnson Stephanie M Crader Jyoti J Watters Gordon S Mitchell Mary Behan |
| author_sort | Keith B Hengen |
| collection | DOAJ |
| description | GABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increases in circulating neurosteroids. ε subunit-containing GABA(A)Rs are insensitive to positive allosteric modulation, thus we hypothesized that pregnant rats increase ε subunit-containing GABA(A)R expression on brainstem neurons of the ventral respiratory column (VRC). In vivo, pregnancy rendered respiratory motor output insensitive to otherwise lethal doses of pentobarbital, a barbiturate previously used to categorize the ε subunit. Using electrode array recordings in vitro, we demonstrated that putative respiratory neurons of the preBötzinger Complex (preBötC) were also rendered insensitive to the effects of pentobarbital during pregnancy, but unit activity in the VRC was rapidly inhibited by the GABA(A)R agonist, muscimol. VRC unit activity from virgin and post-partum females was potently inhibited by both pentobarbital and muscimol. Brainstem ε subunit mRNA and protein levels were increased in pregnant rats, and GABA(A)R ε subunit expression co-localized with a marker of rhythm generating neurons (neurokinin 1 receptors) in the preBötC. These data support the hypothesis that pregnancy renders respiratory motor output and respiratory neuron activity insensitive to barbiturates, most likely via increased ε subunit-containing GABA(A)R expression on respiratory rhythm-generating neurons. Increased ε subunit expression may be critical to preserve respiratory function (and life) despite increased neurosteroid levels during pregnancy. |
| first_indexed | 2024-12-19T19:57:18Z |
| format | Article |
| id | doaj.art-0f737e175be6440bb5eeb9c7511be33a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T19:57:18Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0f737e175be6440bb5eeb9c7511be33a2022-12-21T20:07:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e3060810.1371/journal.pone.0030608Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy.Keith B HengenNathan R NelsonKyle M StangStephen M JohnsonStephanie M CraderJyoti J WattersGordon S MitchellMary BehanGABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increases in circulating neurosteroids. ε subunit-containing GABA(A)Rs are insensitive to positive allosteric modulation, thus we hypothesized that pregnant rats increase ε subunit-containing GABA(A)R expression on brainstem neurons of the ventral respiratory column (VRC). In vivo, pregnancy rendered respiratory motor output insensitive to otherwise lethal doses of pentobarbital, a barbiturate previously used to categorize the ε subunit. Using electrode array recordings in vitro, we demonstrated that putative respiratory neurons of the preBötzinger Complex (preBötC) were also rendered insensitive to the effects of pentobarbital during pregnancy, but unit activity in the VRC was rapidly inhibited by the GABA(A)R agonist, muscimol. VRC unit activity from virgin and post-partum females was potently inhibited by both pentobarbital and muscimol. Brainstem ε subunit mRNA and protein levels were increased in pregnant rats, and GABA(A)R ε subunit expression co-localized with a marker of rhythm generating neurons (neurokinin 1 receptors) in the preBötC. These data support the hypothesis that pregnancy renders respiratory motor output and respiratory neuron activity insensitive to barbiturates, most likely via increased ε subunit-containing GABA(A)R expression on respiratory rhythm-generating neurons. Increased ε subunit expression may be critical to preserve respiratory function (and life) despite increased neurosteroid levels during pregnancy.http://europepmc.org/articles/PMC3269439?pdf=render |
| spellingShingle | Keith B Hengen Nathan R Nelson Kyle M Stang Stephen M Johnson Stephanie M Crader Jyoti J Watters Gordon S Mitchell Mary Behan Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. PLoS ONE |
| title | Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. |
| title_full | Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. |
| title_fullStr | Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. |
| title_full_unstemmed | Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. |
| title_short | Increased GABA(A) receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. |
| title_sort | increased gaba a receptor ε subunit expression on ventral respiratory column neurons protects breathing during pregnancy |
| url | http://europepmc.org/articles/PMC3269439?pdf=render |
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