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

Abstract: 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 basa...

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Detalles Bibliográficos
Autores principales: Nobles, Muriel, Montaigne, David, Sebastian, Sonia, Birnbaumer, Lutz, Tinker, Andrew
Otros Autores: 0000-0002-7654-2565
Formato: Artículo
Lenguaje:Inglés
Publicado: American Physiological Society 2019
Materias:
POTASIO
RITMO CARDIACO
ARRITMIA
CORAZON
FIBRILACION AURICULAR
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8707
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8707
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic POTASIO
RITMO CARDIACO
ARRITMIA
CORAZON
FIBRILACION AURICULAR
spellingShingle POTASIO
RITMO CARDIACO
ARRITMIA
CORAZON
FIBRILACION AURICULAR
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
topic_facet POTASIO
RITMO CARDIACO
ARRITMIA
CORAZON
FIBRILACION AURICULAR
description Abstract: 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.
author2 0000-0002-7654-2565
author_facet 0000-0002-7654-2565
Nobles, Muriel
Montaigne, David
Sebastian, Sonia
Birnbaumer, Lutz
Tinker, Andrew
format Artículo
author Nobles, Muriel
Montaigne, David
Sebastian, Sonia
Birnbaumer, Lutz
Tinker, Andrew
author_sort Nobles, Muriel
title Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying K+ currents in adult murine atria
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
publisher American Physiological Society
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8707
work_keys_str_mv AT noblesmuriel differentialeffectsofinhibitorygproteinisoformsongproteingatedinwardlyrectifyingkcurrentsinadultmurineatria
AT montaignedavid differentialeffectsofinhibitorygproteinisoformsongproteingatedinwardlyrectifyingkcurrentsinadultmurineatria
AT sebastiansonia differentialeffectsofinhibitorygproteinisoformsongproteingatedinwardlyrectifyingkcurrentsinadultmurineatria
AT birnbaumerlutz differentialeffectsofinhibitorygproteinisoformsongproteingatedinwardlyrectifyingkcurrentsinadultmurineatria
AT tinkerandrew differentialeffectsofinhibitorygproteinisoformsongproteingatedinwardlyrectifyingkcurrentsinadultmurineatria
bdutipo_str Repositorios
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