Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium

Detalhes bibliográficos
Autor(a) principal: Antunes, Gabriela
Data de Publicação: 2014
Outros Autores: Sebastião, Ana M, Simoes de Souza, Fabio Marques
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/55358
Resumo: Copyright: © 2014 Antunes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id RCAP_b0ec3ed9d2cc3cca70971650b4ba62a6
oai_identifier_str oai:repositorio.ul.pt:10451/55358
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Mechanisms of regulation of olfactory transduction and adaptation in the olfactory ciliumCopyright: © 2014 Antunes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Olfactory adaptation is a fundamental process for the functioning of the olfactory system, but the underlying mechanisms regulating its occurrence in intact olfactory sensory neurons (OSNs) are not fully understood. In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). We used odorant stimulation and electroolfactogram (EOG) recordings of the olfactory epithelium treated with pharmacological blockers to study the molecular mechanisms regulating the occurrence of adaptation in OSNs. EOG responses to paired-pulses of odorants showed that inhibition of phosphodiesterases (PDEs) and phosphatases enhanced the levels of STA in the olfactory epithelium, and this effect was mimicked by blocking vesicle exocytosis and reduced by blocking cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and vesicle endocytosis. These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca(2+))-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca(2+), and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca(2+) response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control GPCR cycling and tune the levels of second messengers in OSNs, and not only by CNG channel desensitization as previously thought.The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PCOFUND-GA-2009-246542 and from the Foundation for Science and Technology of Portugal. GA has received the fellowship SFRH/BI/52112/2013 of the Foundation for Science and Technology of Portugal.PLOSRepositório da Universidade de LisboaAntunes, GabrielaSebastião, Ana MSimoes de Souza, Fabio Marques2022-12-06T14:48:59Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/55358engPLoS One. 2014 Aug 21;9(8):e10553110.1371/journal.pone.01055311932-6203info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:02:15Zoai:repositorio.ul.pt:10451/55358Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:06:01.073866Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
title Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
spellingShingle Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
Antunes, Gabriela
title_short Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
title_full Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
title_fullStr Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
title_full_unstemmed Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
title_sort Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium
author Antunes, Gabriela
author_facet Antunes, Gabriela
Sebastião, Ana M
Simoes de Souza, Fabio Marques
author_role author
author2 Sebastião, Ana M
Simoes de Souza, Fabio Marques
author2_role author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Antunes, Gabriela
Sebastião, Ana M
Simoes de Souza, Fabio Marques
description Copyright: © 2014 Antunes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
2022-12-06T14:48:59Z
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://hdl.handle.net/10451/55358
url http://hdl.handle.net/10451/55358
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS One. 2014 Aug 21;9(8):e105531
10.1371/journal.pone.0105531
1932-6203
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134612855717888

Registros relacionados