Proton detection and breathing regulation by the retrotrapezoid nucleus
Abstract We discuss recent evidence which suggests that the principal central respiratory chemoreceptors are located within the retrotrapezoid nucleus (RTN) and that RTN neurons are directly sensitive to [H+]. RTN neurons are glutamatergic. In vitro, their activation by [H+] requires expression of a...
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2016
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| Online Access: | http://hdl.handle.net/10725/4561 https://doi.org/10.1113/JP271480 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP271480 |
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| _version_ | 1864513464012111872 |
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| author | Guyenet, Patrice G. |
| author2 | Bayliss, Douglas A. Stornetta, Ruth L. Ludwig, Marie-Gabrielle Kumar, Natasha N. Shi, Yingtang Burke, Peter G. R. Kanbar, Roy Basting, Tyler M. Holloway, Benjamin B. Wenker, Ian C. |
| author2_role | author author author author author author author author author author |
| author_facet | Guyenet, Patrice G. Bayliss, Douglas A. Stornetta, Ruth L. Ludwig, Marie-Gabrielle Kumar, Natasha N. Shi, Yingtang Burke, Peter G. R. Kanbar, Roy Basting, Tyler M. Holloway, Benjamin B. Wenker, Ian C. |
| author_role | author |
| dc.creator.none.fl_str_mv | Guyenet, Patrice G. Bayliss, Douglas A. Stornetta, Ruth L. Ludwig, Marie-Gabrielle Kumar, Natasha N. Shi, Yingtang Burke, Peter G. R. Kanbar, Roy Basting, Tyler M. Holloway, Benjamin B. Wenker, Ian C. |
| dc.date.none.fl_str_mv | 2016-10-11T08:55:40Z 2016-10-11T08:55:40Z 2016 2016-10-11 |
| dc.identifier.none.fl_str_mv | 0022-3751 http://hdl.handle.net/10725/4561 https://doi.org/10.1113/JP271480 Guyenet, P. G., Bayliss, D. A., Stornetta, R. L., Ludwig, M. G., Kumar, N. N., Shi, Y., ... & Wenker, I. C. (2016). Proton detection and breathing regulation by the retrotrapezoid nucleus. The Journal of physiology 594 (6), 1529-1551 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP271480 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | The Journal of Physiology |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Proton detection and breathing regulation by the retrotrapezoid nucleus |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Abstract We discuss recent evidence which suggests that the principal central respiratory chemoreceptors are located within the retrotrapezoid nucleus (RTN) and that RTN neurons are directly sensitive to [H+]. RTN neurons are glutamatergic. In vitro, their activation by [H+] requires expression of a proton-activated G protein-coupled receptor (GPR4) and a proton-modulated potassium channel (TASK-2) whose transcripts are undetectable in astrocytes and the rest of the lower brainstem respiratory network. The pH response of RTN neurons is modulated by surrounding astrocytes but genetic deletion of RTN neurons or deletion of both GPR4 and TASK-2 virtually eliminates the central respiratory chemoreflex. Thus, although this reflex is regulated by innumerable brain pathways, it seems to operate predominantly by modulating the discharge rate of RTN neurons, and the activation of RTN neurons by hypercapnia may ultimately derive from their intrinsic pH sensitivity. RTN neurons increase lung ventilation by stimulating multiple aspects of breathing simultaneously. They stimulate breathing about equally during quiet wake and non-rapid eye movement (REM) sleep, and to a lesser degree during REM sleep. The activity of RTN neurons is regulated by inhibitory feedback and by excitatory inputs, notably from the carotid bodies. The latter input operates during normo- or hypercapnia but fails to activate RTN neurons under hypocapnic conditions. RTN inhibition probably limits the degree of hyperventilation produced by hypocapnic hypoxia. RTN neurons are also activated by inputs from serotonergic neurons and hypothalamic neurons. The absence of RTN neurons probably underlies the sleep apnoea and lack of chemoreflex that characterize congenital central hypoventilation syndrome. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_99f253f6acca24fe2f635bd181063da7 |
| identifier_str_mv | 0022-3751 Guyenet, P. G., Bayliss, D. A., Stornetta, R. L., Ludwig, M. G., Kumar, N. N., Shi, Y., ... & Wenker, I. C. (2016). Proton detection and breathing regulation by the retrotrapezoid nucleus. The Journal of physiology 594 (6), 1529-1551 |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/4561 |
| publishDate | 2016 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Proton detection and breathing regulation by the retrotrapezoid nucleusGuyenet, Patrice G.Bayliss, Douglas A.Stornetta, Ruth L.Ludwig, Marie-GabrielleKumar, Natasha N.Shi, YingtangBurke, Peter G. R.Kanbar, RoyBasting, Tyler M.Holloway, Benjamin B.Wenker, Ian C.Abstract We discuss recent evidence which suggests that the principal central respiratory chemoreceptors are located within the retrotrapezoid nucleus (RTN) and that RTN neurons are directly sensitive to [H+]. RTN neurons are glutamatergic. In vitro, their activation by [H+] requires expression of a proton-activated G protein-coupled receptor (GPR4) and a proton-modulated potassium channel (TASK-2) whose transcripts are undetectable in astrocytes and the rest of the lower brainstem respiratory network. The pH response of RTN neurons is modulated by surrounding astrocytes but genetic deletion of RTN neurons or deletion of both GPR4 and TASK-2 virtually eliminates the central respiratory chemoreflex. Thus, although this reflex is regulated by innumerable brain pathways, it seems to operate predominantly by modulating the discharge rate of RTN neurons, and the activation of RTN neurons by hypercapnia may ultimately derive from their intrinsic pH sensitivity. RTN neurons increase lung ventilation by stimulating multiple aspects of breathing simultaneously. They stimulate breathing about equally during quiet wake and non-rapid eye movement (REM) sleep, and to a lesser degree during REM sleep. The activity of RTN neurons is regulated by inhibitory feedback and by excitatory inputs, notably from the carotid bodies. The latter input operates during normo- or hypercapnia but fails to activate RTN neurons under hypocapnic conditions. RTN inhibition probably limits the degree of hyperventilation produced by hypocapnic hypoxia. RTN neurons are also activated by inputs from serotonergic neurons and hypothalamic neurons. The absence of RTN neurons probably underlies the sleep apnoea and lack of chemoreflex that characterize congenital central hypoventilation syndrome.PublishedN/A2016-10-11T08:55:40Z2016-10-11T08:55:40Z20162016-10-11Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0022-3751http://hdl.handle.net/10725/4561https://doi.org/10.1113/JP271480Guyenet, P. G., Bayliss, D. A., Stornetta, R. L., Ludwig, M. G., Kumar, N. N., Shi, Y., ... & Wenker, I. C. (2016). Proton detection and breathing regulation by the retrotrapezoid nucleus. The Journal of physiology 594 (6), 1529-1551http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP271480enThe Journal of Physiologyinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/45612021-03-19T10:00:50Z |
| spellingShingle | Proton detection and breathing regulation by the retrotrapezoid nucleus Guyenet, Patrice G. |
| status_str | publishedVersion |
| title | Proton detection and breathing regulation by the retrotrapezoid nucleus |
| title_full | Proton detection and breathing regulation by the retrotrapezoid nucleus |
| title_fullStr | Proton detection and breathing regulation by the retrotrapezoid nucleus |
| title_full_unstemmed | Proton detection and breathing regulation by the retrotrapezoid nucleus |
| title_short | Proton detection and breathing regulation by the retrotrapezoid nucleus |
| title_sort | Proton detection and breathing regulation by the retrotrapezoid nucleus |
| url | http://hdl.handle.net/10725/4561 https://doi.org/10.1113/JP271480 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP271480 |