| First Author | Opel A | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 31 | Pages | 19233-44 |
| PubMed ID | 26088132 | Mgi Jnum | J:224603 |
| Mgi Id | MGI:5688414 | Doi | 10.1074/jbc.M115.666719 |
| Citation | Opel A, et al. (2015) Absence of the Regulator of G-protein Signaling, RGS4, Predisposes to Atrial Fibrillation and Is Associated with Abnormal Calcium Handling. J Biol Chem 290(31):19233-44 |
| abstractText | The description of potential molecular substrates for predisposition to atrial fibrillation (AF) is incomplete, and it is unknown what role regulators of G-protein signaling might play. We address whether the attenuation of RGS4 function may promote AF and the mechanism through which this occurs. For this purpose, we studied a mouse with global genetic deletion of RGS4 (RGS4(-/-)) and the normal littermate controls (RGS4(+/+)). In vivo electrophysiology using atrial burst pacing revealed that mice with global RGS4 deletion developed AF more frequently than control littermates. Isolated atrial cells from RGS4(-/-) mice show an increase in Ca(2+) spark frequency under basal conditions and after the addition of endothelin-1 and abnormal spontaneous Ca(2+) release events after field stimulation. Isolated left atria studied on a multielectrode array revealed modest changes in path length for re-entry but abnormal electrical events after a pacing train in RGS4(-/-) mice. RGS4 deletion results in a predisposition to atrial fibrillation from enhanced activity in the Galphaq/11-IP3 pathway, resulting in abnormal Ca(2+) release and corresponding electrical events. |
