The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.neuroscience.2018.03.031 http://hdl.handle.net/11449/176307 |
Resumo: | The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an “accelerator” whereby hypercapnic acidosis causes an inhibition of K+ channels or activation of Na+ and Ca+2 channels to depolarize CO2-sensitive neurons. Nevertheless, it is still unknown if this “accelerator” mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons. Hypercapnic acidosis activates L-type Ca2+ channels and large conductance Ca-activated K+ (BK) channels, which function as a “brake” on the chemosensitive response of LC neurons. Our findings indicate that both Ca2+ and BK currents develop over the first 2 weeks of postnatal life in rat LC slices and that this brake pathway may cause the developmental decrease in the chemosensitive firing rate response of LC neurons to hypercapnic acidosis. Inhibition of this brake by paxilline (BK channel inhibitor) returns the magnitude of the chemosensitive firing rate response from LC neurons in rats older than P10 to high values similar to those in LC neurons from younger rats. Inhibition of BK channels in LC neurons by bilateral injections of paxilline into the LC results in a significant increase in the hypercapnic ventilatory response of adult rats. Our findings indicate that a BK channel-based braking system helps to determine the chemosensitive respiratory drive of LC neurons and contributes to the hypercapnic ventilatory response. Perhaps, abnormalities of this braking system could result in hypercapnia-induced respiratory disorders and panic responses. |
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The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Ratscentral control of breathingdevelopmentneuronal acid sensingpanic disorderpaxillineThe cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an “accelerator” whereby hypercapnic acidosis causes an inhibition of K+ channels or activation of Na+ and Ca+2 channels to depolarize CO2-sensitive neurons. Nevertheless, it is still unknown if this “accelerator” mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons. Hypercapnic acidosis activates L-type Ca2+ channels and large conductance Ca-activated K+ (BK) channels, which function as a “brake” on the chemosensitive response of LC neurons. Our findings indicate that both Ca2+ and BK currents develop over the first 2 weeks of postnatal life in rat LC slices and that this brake pathway may cause the developmental decrease in the chemosensitive firing rate response of LC neurons to hypercapnic acidosis. Inhibition of this brake by paxilline (BK channel inhibitor) returns the magnitude of the chemosensitive firing rate response from LC neurons in rats older than P10 to high values similar to those in LC neurons from younger rats. Inhibition of BK channels in LC neurons by bilateral injections of paxilline into the LC results in a significant increase in the hypercapnic ventilatory response of adult rats. Our findings indicate that a BK channel-based braking system helps to determine the chemosensitive respiratory drive of LC neurons and contributes to the hypercapnic ventilatory response. Perhaps, abnormalities of this braking system could result in hypercapnia-induced respiratory disorders and panic responses.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Heart, Lung, and Blood InstituteWright State UniversityDepartment of Neuroscience Cell Biology and Physiology Wright State University Boonshoft School of Medicine, 3640 Colonel Glenn HighwayDepartment of Animal Morphology and Physiology Sao Paulo State University – UNESP/FCAV, JaboticabalDepartment of Animal Morphology and Physiology Sao Paulo State University – UNESP/FCAV, JaboticabalFAPESP: 2010/06210-9FAPESP: 2016/24577-3National Heart, Lung, and Blood Institute: R01 HL-56683Boonshoft School of MedicineUniversidade Estadual Paulista (Unesp)Imber, Ann N.Patrone, Luis G.A. [UNESP]Li, Ke-YongGargaglioni, Luciane H. [UNESP]Putnam, Robert W.2018-12-11T17:20:03Z2018-12-11T17:20:03Z2018-06-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article59-78application/pdfhttp://dx.doi.org/10.1016/j.neuroscience.2018.03.031Neuroscience, v. 381, p. 59-78.1873-75440306-4522http://hdl.handle.net/11449/17630710.1016/j.neuroscience.2018.03.0312-s2.0-850467738122-s2.0-85046773812.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeuroscience1,602info:eu-repo/semantics/openAccess2023-12-29T06:19:32Zoai:repositorio.unesp.br:11449/176307Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-29T06:19:32Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats |
title |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats |
spellingShingle |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats Imber, Ann N. central control of breathing development neuronal acid sensing panic disorder paxilline |
title_short |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats |
title_full |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats |
title_fullStr |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats |
title_full_unstemmed |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats |
title_sort |
The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats |
author |
Imber, Ann N. |
author_facet |
Imber, Ann N. Patrone, Luis G.A. [UNESP] Li, Ke-Yong Gargaglioni, Luciane H. [UNESP] Putnam, Robert W. |
author_role |
author |
author2 |
Patrone, Luis G.A. [UNESP] Li, Ke-Yong Gargaglioni, Luciane H. [UNESP] Putnam, Robert W. |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Boonshoft School of Medicine Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Imber, Ann N. Patrone, Luis G.A. [UNESP] Li, Ke-Yong Gargaglioni, Luciane H. [UNESP] Putnam, Robert W. |
dc.subject.por.fl_str_mv |
central control of breathing development neuronal acid sensing panic disorder paxilline |
topic |
central control of breathing development neuronal acid sensing panic disorder paxilline |
description |
The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an “accelerator” whereby hypercapnic acidosis causes an inhibition of K+ channels or activation of Na+ and Ca+2 channels to depolarize CO2-sensitive neurons. Nevertheless, it is still unknown if this “accelerator” mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons. Hypercapnic acidosis activates L-type Ca2+ channels and large conductance Ca-activated K+ (BK) channels, which function as a “brake” on the chemosensitive response of LC neurons. Our findings indicate that both Ca2+ and BK currents develop over the first 2 weeks of postnatal life in rat LC slices and that this brake pathway may cause the developmental decrease in the chemosensitive firing rate response of LC neurons to hypercapnic acidosis. Inhibition of this brake by paxilline (BK channel inhibitor) returns the magnitude of the chemosensitive firing rate response from LC neurons in rats older than P10 to high values similar to those in LC neurons from younger rats. Inhibition of BK channels in LC neurons by bilateral injections of paxilline into the LC results in a significant increase in the hypercapnic ventilatory response of adult rats. Our findings indicate that a BK channel-based braking system helps to determine the chemosensitive respiratory drive of LC neurons and contributes to the hypercapnic ventilatory response. Perhaps, abnormalities of this braking system could result in hypercapnia-induced respiratory disorders and panic responses. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:20:03Z 2018-12-11T17:20:03Z 2018-06-15 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.neuroscience.2018.03.031 Neuroscience, v. 381, p. 59-78. 1873-7544 0306-4522 http://hdl.handle.net/11449/176307 10.1016/j.neuroscience.2018.03.031 2-s2.0-85046773812 2-s2.0-85046773812.pdf |
url |
http://dx.doi.org/10.1016/j.neuroscience.2018.03.031 http://hdl.handle.net/11449/176307 |
identifier_str_mv |
Neuroscience, v. 381, p. 59-78. 1873-7544 0306-4522 10.1016/j.neuroscience.2018.03.031 2-s2.0-85046773812 2-s2.0-85046773812.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Neuroscience 1,602 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
59-78 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1799965447008813056 |