Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit

Autores
Martín, Pedro; Moncada, Melisa; Castillo, Karen Noel; Orsi, Federico; Ducca, Gerónimo Marcelo; Fernández, José Manuel; González, Carlos; Milesi, Verónica
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the β1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary β1 subunit.
Fil: Martín, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Moncada, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Castillo, Karen Noel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Valparaíso; Chile
Fil: Orsi, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Ducca, Gerónimo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Fernández, José Manuel. Universitat Pompeu Fabra; España
Fil: González, Carlos. Universidad de Valparaíso; Chile
Fil: Milesi, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Materia
ARACHIDONIC ACID
BIG CONDUCTANCE CALCIUM AND VOLTAGE ACTIVATED POTASSIUM CHANNEL, BK
FATTY ACID
MAXIK
SLO1
VOLTAGE SENSOR
Β-AUXILIARY SUBUNITS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/180734
Acceder
id CONICETDig_6c8e11a76e711ae96c2d83627c917981
oai_identifier_str oai:ri.conicet.gov.ar:11336/180734
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunitMartín, PedroMoncada, MelisaCastillo, Karen NoelOrsi, FedericoDucca, Gerónimo MarceloFernández, José ManuelGonzález, CarlosMilesi, VerónicaARACHIDONIC ACIDBIG CONDUCTANCE CALCIUM AND VOLTAGE ACTIVATED POTASSIUM CHANNEL, BKFATTY ACIDMAXIKSLO1VOLTAGE SENSORΒ-AUXILIARY SUBUNITShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the β1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary β1 subunit.Fil: Martín, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Moncada, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Castillo, Karen Noel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Valparaíso; ChileFil: Orsi, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ducca, Gerónimo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Fernández, José Manuel. Universitat Pompeu Fabra; EspañaFil: González, Carlos. Universidad de Valparaíso; ChileFil: Milesi, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaElsevier Science2021-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/180734Martín, Pedro; Moncada, Melisa; Castillo, Karen Noel; Orsi, Federico; Ducca, Gerónimo Marcelo; et al.; Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1863; 9; 9-2021; 1-90005-27361879-2642CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0005273621000018info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamem.2021.183550info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:13Zoai:ri.conicet.gov.ar:11336/180734instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:13.421CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
title Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
spellingShingle Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
Martín, Pedro
ARACHIDONIC ACID
BIG CONDUCTANCE CALCIUM AND VOLTAGE ACTIVATED POTASSIUM CHANNEL, BK
FATTY ACID
MAXIK
SLO1
VOLTAGE SENSOR
Β-AUXILIARY SUBUNITS
title_short Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
title_full Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
title_fullStr Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
title_full_unstemmed Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
title_sort Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit
dc.creator.none.fl_str_mv Martín, Pedro
Moncada, Melisa
Castillo, Karen Noel
Orsi, Federico
Ducca, Gerónimo Marcelo
Fernández, José Manuel
González, Carlos
Milesi, Verónica
author Martín, Pedro
author_facet Martín, Pedro
Moncada, Melisa
Castillo, Karen Noel
Orsi, Federico
Ducca, Gerónimo Marcelo
Fernández, José Manuel
González, Carlos
Milesi, Verónica
author_role author
author2 Moncada, Melisa
Castillo, Karen Noel
Orsi, Federico
Ducca, Gerónimo Marcelo
Fernández, José Manuel
González, Carlos
Milesi, Verónica
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ARACHIDONIC ACID
BIG CONDUCTANCE CALCIUM AND VOLTAGE ACTIVATED POTASSIUM CHANNEL, BK
FATTY ACID
MAXIK
SLO1
VOLTAGE SENSOR
Β-AUXILIARY SUBUNITS
topic ARACHIDONIC ACID
BIG CONDUCTANCE CALCIUM AND VOLTAGE ACTIVATED POTASSIUM CHANNEL, BK
FATTY ACID
MAXIK
SLO1
VOLTAGE SENSOR
Β-AUXILIARY SUBUNITS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the β1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary β1 subunit.
Fil: Martín, Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Moncada, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Castillo, Karen Noel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Valparaíso; Chile
Fil: Orsi, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Ducca, Gerónimo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Fernández, José Manuel. Universitat Pompeu Fabra; España
Fil: González, Carlos. Universidad de Valparaíso; Chile
Fil: Milesi, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
description Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the β1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary β1 subunit.
publishDate 2021
dc.date.none.fl_str_mv 2021-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/180734
Martín, Pedro; Moncada, Melisa; Castillo, Karen Noel; Orsi, Federico; Ducca, Gerónimo Marcelo; et al.; Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1863; 9; 9-2021; 1-9
0005-2736
1879-2642
CONICET Digital
CONICET
url http://hdl.handle.net/11336/180734
identifier_str_mv Martín, Pedro; Moncada, Melisa; Castillo, Karen Noel; Orsi, Federico; Ducca, Gerónimo Marcelo; et al.; Arachidonic acid effect on the allosteric gating mechanism of BK (Slo1) channels associated with the β1 subunit; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1863; 9; 9-2021; 1-9
0005-2736
1879-2642
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0005273621000018
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamem.2021.183550
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269994271899648
score 13.13397

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