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

Página do item simplificado
dc.contributor.authorImber, Ann N.
dc.contributor.authorPatrone, Luis G.A. [UNESP]
dc.contributor.authorLi, Ke-Yong
dc.contributor.authorGargaglioni, Luciane H. [UNESP]
dc.contributor.authorPutnam, Robert W.
dc.contributor.institutionBoonshoft School of Medicine
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-12-11T17:20:03Z
dc.date.available2018-12-11T17:20:03Z
dc.date.issued2018-06-15
dc.description.abstractThe 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.en
dc.description.affiliationDepartment of Neuroscience Cell Biology and Physiology Wright State University Boonshoft School of Medicine, 3640 Colonel Glenn Highway
dc.description.affiliationDepartment of Animal Morphology and Physiology Sao Paulo State University – UNESP/FCAV, Jaboticabal
dc.description.affiliationUnespDepartment of Animal Morphology and Physiology Sao Paulo State University – UNESP/FCAV, Jaboticabal
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipNational Heart, Lung, and Blood Institute
dc.description.sponsorshipWright State University
dc.description.sponsorshipIdFAPESP: 2010/06210-9
dc.description.sponsorshipIdFAPESP: 2016/24577-3
dc.description.sponsorshipIdNational Heart, Lung, and Blood Institute: R01 HL-56683
dc.format.extent59-78
dc.identifierhttp://dx.doi.org/10.1016/j.neuroscience.2018.03.031
dc.identifier.citationNeuroscience, v. 381, p. 59-78.
dc.identifier.doi10.1016/j.neuroscience.2018.03.031
dc.identifier.file2-s2.0-85046773812.pdf
dc.identifier.issn1873-7544
dc.identifier.issn0306-4522
dc.identifier.scopus2-s2.0-85046773812
dc.identifier.urihttp://hdl.handle.net/11449/176307
dc.language.isoeng
dc.relation.ispartofNeuroscience
dc.relation.ispartofsjr1,602
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectcentral control of breathing
dc.subjectdevelopment
dc.subjectneuronal acid sensing
dc.subjectpanic disorder
dc.subjectpaxilline
dc.titleThe Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Ratsen
dc.typeArtigo

Arquivos

Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
2-s2.0-85046773812.pdf
Tamanho:
4.26 MB
Formato:
Adobe Portable Document Format
Descrição:
Baixar

Coleções

Artigos - Morfologia e Fisiologia Animal - FCAV