The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats

Detalhes bibliográficos
Autor(a) principal: Imber, Ann N.
Data de Publicação: 2018
Outros Autores: Patrone, Luis G.A. [UNESP], Li, Ke-Yong, Gargaglioni, Luciane H. [UNESP], Putnam, Robert W.
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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spelling 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)
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