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
• Fuente: American Journal of Physiology-Cell Physiology. 2018;314(5):C616-C626
• Materia: POTASIO; RITMO CARDIACO; ARRITMIA; CORAZON; FIBRILACION AURICULAR
• Institución: Pontificia Universidad Católica Argentina

Fil: Nobles, Muriel. Barts and the London School of Medicine and Dentistry. William Harvey Research Institute. The Heart Centre; Reino Unido
Fil: Montaigne, David. Centre Hospitalier Régional Universitaire de Lille; Francia
Fil: Montaigne, David. Université Lille 2; Francia
Fil: Sebastian, Sonia. Barts and the London School of Medicine and Dentistry. William Harvey Research Institute. The Heart Centre; Reino Unido
Fil: Sebastian, Sonia. Institut National de la Santé et de la Recherche Médicale; Francia
Fil: Sebastian, Sonia. European Genomic Institute for Diabetes; Francia
Fil: Sebastian, Sonia. Institut Pasteur de Lille; Francia
Fil: Birnbaumer, Lutz. Research Triangle Park. National Institute of Environmental Health Sciences. Division of Intramural Research; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Tinker, Andrew. Barts and the London School of Medicine and Dentistry. William Harvey Research Institute. The Heart Centre; Reino Unido
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.