CONICET | Buscador de Institutos y Recursos Humanos

G-protein gated inwardly rectifying K+21 (GIRK) channels are the major inwardlyrectifying K+22 currents in cardiac atrial myocytes and an important determinant of atrial23 electrophysiology. Inhibitory G-protein alpha subunits can both mediate activation via24 acetylcholine but can also supress basal currents in the absence of agonist. We studied this25 phenomenon using whole cell patch clamping in murine atria from mice with global genetic26 deletion of Gi2, combined deletion of Gi1/Gi3 and littermate controls. We found that mice27 with deletion of Gi2 had increased basal and agonist activated currents particularly in the28 right atria whilst in contrast those with Gi1/Gi3 deletion had reduced currents. Mice with29 global genetic deletion of Gi2 had decreased action potential duration. Tissue preparations30 of the left atria studied with a multielectrode array from Gi2 knockout mice showed a31 shorter effective refractory period, with no change in conduction velocity, than littermate32 controls. Transcriptional studies revealed increased expression of GIRK channel subunit33 genes in Gi2 knockout mice. Thus different G-protein isoforms have differential effects on34 GIRK channel behaviour and paradoxically Gi2 acts to increase basal and agonist activated35 GIRK currents. Deletion of Gi2 is potentially proarrhythmic in the atria.