Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria

Autores
Nobles, Muriel; Montaigne, David; Sebastian, Sonia; Birnbaumer, Lutz; Tinker, Andrew
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
G protein-gated inwardly rectifying K+ (GIRK) channels are the major inwardly rectifying K+ currents in cardiac atrial myocytes and an important determinant of atrial electrophysiology. Inhibitory G protein α-subunits can both mediate activation via acetylcholine but can also suppress basal currents in the absence of agonist. We studied this phenomenon using whole cell patch clamping in murine atria from mice with global genetic deletion of Gαi2, combined deletion of Gαi1/Gαi3, and littermate controls. We found that mice with deletion of Gαi2 had increased basal and agonist-activated currents, particularly in the right atria while in contrast those with Gαi1/Gαi3 deletion had reduced currents. Mice with global genetic deletion of Gαi2 had decreased action potential duration. Tissue preparations of the left atria studied with a multielectrode array from Gαi2 knockout mice showed a shorter effective refractory period, with no change in conduction velocity, than littermate controls. Transcriptional studies revealed increased expression of GIRK channel subunit genes in Gαi2 knockout mice. Thus different G protein isoforms have differential effects on GIRK channel behavior and paradoxically Gαi2 act to increase basal and agonist-activated GIRK currents. Deletion of Gαi2 is potentially proarrhythmic in the atria.
Fil: Nobles, Muriel. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino Unido
Fil: Montaigne, David. Université Lille; Francia
Fil: Sebastian, Sonia. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino Unido
Fil: Birnbaumer, Lutz. National Institute Of Environmental Health Sciences; . Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tinker, Andrew. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino Unido
Materia
ATRIA
ELECTROPHYSIOLOGY
G PROTEIN-GATED POTASSIUM CHANNEL
INHIBITORY HETEROTRIMERIC G PROTEIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/98872
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98872
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atriaNobles, MurielMontaigne, DavidSebastian, SoniaBirnbaumer, LutzTinker, AndrewATRIAELECTROPHYSIOLOGYG PROTEIN-GATED POTASSIUM CHANNELINHIBITORY HETEROTRIMERIC G PROTEINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1G protein-gated inwardly rectifying K+ (GIRK) channels are the major inwardly rectifying K+ currents in cardiac atrial myocytes and an important determinant of atrial electrophysiology. Inhibitory G protein α-subunits can both mediate activation via acetylcholine but can also suppress basal currents in the absence of agonist. We studied this phenomenon using whole cell patch clamping in murine atria from mice with global genetic deletion of Gαi2, combined deletion of Gαi1/Gαi3, and littermate controls. We found that mice with deletion of Gαi2 had increased basal and agonist-activated currents, particularly in the right atria while in contrast those with Gαi1/Gαi3 deletion had reduced currents. Mice with global genetic deletion of Gαi2 had decreased action potential duration. Tissue preparations of the left atria studied with a multielectrode array from Gαi2 knockout mice showed a shorter effective refractory period, with no change in conduction velocity, than littermate controls. Transcriptional studies revealed increased expression of GIRK channel subunit genes in Gαi2 knockout mice. Thus different G protein isoforms have differential effects on GIRK channel behavior and paradoxically Gαi2 act to increase basal and agonist-activated GIRK currents. Deletion of Gαi2 is potentially proarrhythmic in the atria.Fil: Nobles, Muriel. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino UnidoFil: Montaigne, David. Université Lille; FranciaFil: Sebastian, Sonia. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino UnidoFil: Birnbaumer, Lutz. National Institute Of Environmental Health Sciences; . Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tinker, Andrew. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino UnidoAmerican Physiological Society2018-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/98872Nobles, Muriel; Montaigne, David; Sebastian, Sonia; Birnbaumer, Lutz; Tinker, Andrew; Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria; American Physiological Society; American journal of physiology. Cell physiology; 314; 5; 5-2018; C616-C6261522-1563CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.physiology.org/doi/10.1152/ajpcell.00271.2016info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00271.2016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:43:52Zoai:ri.conicet.gov.ar:11336/98872instacron: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:34982025-09-29 09:43:52.989CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
title Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
spellingShingle Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
Nobles, Muriel
ATRIA
ELECTROPHYSIOLOGY
G PROTEIN-GATED POTASSIUM CHANNEL
INHIBITORY HETEROTRIMERIC G PROTEIN
title_short Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
title_full Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
title_fullStr Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
title_full_unstemmed Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
title_sort Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria
dc.creator.none.fl_str_mv Nobles, Muriel
Montaigne, David
Sebastian, Sonia
Birnbaumer, Lutz
Tinker, Andrew
author Nobles, Muriel
author_facet Nobles, Muriel
Montaigne, David
Sebastian, Sonia
Birnbaumer, Lutz
Tinker, Andrew
author_role author
author2 Montaigne, David
Sebastian, Sonia
Birnbaumer, Lutz
Tinker, Andrew
author2_role author
author
author
author
dc.subject.none.fl_str_mv ATRIA
ELECTROPHYSIOLOGY
G PROTEIN-GATED POTASSIUM CHANNEL
INHIBITORY HETEROTRIMERIC G PROTEIN
topic ATRIA
ELECTROPHYSIOLOGY
G PROTEIN-GATED POTASSIUM CHANNEL
INHIBITORY HETEROTRIMERIC G PROTEIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv G protein-gated inwardly rectifying K+ (GIRK) channels are the major inwardly rectifying K+ currents in cardiac atrial myocytes and an important determinant of atrial electrophysiology. Inhibitory G protein α-subunits can both mediate activation via acetylcholine but can also suppress basal currents in the absence of agonist. We studied this phenomenon using whole cell patch clamping in murine atria from mice with global genetic deletion of Gαi2, combined deletion of Gαi1/Gαi3, and littermate controls. We found that mice with deletion of Gαi2 had increased basal and agonist-activated currents, particularly in the right atria while in contrast those with Gαi1/Gαi3 deletion had reduced currents. Mice with global genetic deletion of Gαi2 had decreased action potential duration. Tissue preparations of the left atria studied with a multielectrode array from Gαi2 knockout mice showed a shorter effective refractory period, with no change in conduction velocity, than littermate controls. Transcriptional studies revealed increased expression of GIRK channel subunit genes in Gαi2 knockout mice. Thus different G protein isoforms have differential effects on GIRK channel behavior and paradoxically Gαi2 act to increase basal and agonist-activated GIRK currents. Deletion of Gαi2 is potentially proarrhythmic in the atria.
Fil: Nobles, Muriel. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino Unido
Fil: Montaigne, David. Université Lille; Francia
Fil: Sebastian, Sonia. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino Unido
Fil: Birnbaumer, Lutz. National Institute Of Environmental Health Sciences; . Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Tinker, Andrew. London School of Medicine and Dentistry; Reino Unido. William Harvey Research Institute; Reino Unido
description G protein-gated inwardly rectifying K+ (GIRK) channels are the major inwardly rectifying K+ currents in cardiac atrial myocytes and an important determinant of atrial electrophysiology. Inhibitory G protein α-subunits can both mediate activation via acetylcholine but can also suppress basal currents in the absence of agonist. We studied this phenomenon using whole cell patch clamping in murine atria from mice with global genetic deletion of Gαi2, combined deletion of Gαi1/Gαi3, and littermate controls. We found that mice with deletion of Gαi2 had increased basal and agonist-activated currents, particularly in the right atria while in contrast those with Gαi1/Gαi3 deletion had reduced currents. Mice with global genetic deletion of Gαi2 had decreased action potential duration. Tissue preparations of the left atria studied with a multielectrode array from Gαi2 knockout mice showed a shorter effective refractory period, with no change in conduction velocity, than littermate controls. Transcriptional studies revealed increased expression of GIRK channel subunit genes in Gαi2 knockout mice. Thus different G protein isoforms have differential effects on GIRK channel behavior and paradoxically Gαi2 act to increase basal and agonist-activated GIRK currents. Deletion of Gαi2 is potentially proarrhythmic in the atria.
publishDate 2018
dc.date.none.fl_str_mv 2018-05
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/11336/98872
Nobles, Muriel; Montaigne, David; Sebastian, Sonia; Birnbaumer, Lutz; Tinker, Andrew; Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria; American Physiological Society; American journal of physiology. Cell physiology; 314; 5; 5-2018; C616-C626
1522-1563
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98872
identifier_str_mv Nobles, Muriel; Montaigne, David; Sebastian, Sonia; Birnbaumer, Lutz; Tinker, Andrew; Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K + currents in adult murine atria; American Physiological Society; American journal of physiology. Cell physiology; 314; 5; 5-2018; C616-C626
1522-1563
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.physiology.org/doi/10.1152/ajpcell.00271.2016
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00271.2016
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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_ 1844613380747296768
score 13.070432

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