| First Author | Posokhova E | Year | 2010 |
| Journal | Circ Res | Volume | 107 |
| Issue | 11 | Pages | 1350-4 |
| PubMed ID | 20884879 | Mgi Jnum | J:178182 |
| Mgi Id | MGI:5297652 | Doi | 10.1161/CIRCRESAHA.110.224212 |
| Citation | Posokhova E, et al. (2010) RGS6/Gss5 complex accelerates IKACh gating kinetics in atrial myocytes and modulates parasympathetic regulation of heart rate. Circ Res 107(11):1350-4 |
| abstractText | RATIONALE: The parasympathetic reduction in heart rate involves the sequential activation of m2 muscarinic cholinergic receptors (m(2)Rs), pertussis toxin-sensitive (Gi/o) heterotrimeric G proteins, and the atrial potassium channel I(KACh). Molecular mechanisms regulating this critical signal transduction pathway are not fully understood. OBJECTIVE: To determine whether the G protein signaling regulator Rgs6/Gbeta5 modulates m(2)R-I(KACh) signaling and cardiac physiology. METHODS AND RESULTS: Cardiac expression of Rgs6, and its interaction with Gbeta5, was demonstrated by immunoblotting and immunoprecipitation. Rgs6(-/-) mice were generated by gene targeting, and the cardiac effects of Rgs6 ablation were analyzed by whole-cell recordings in isolated cardiomyocytes and ECG telemetry. Loss of Rgs6 yielded profound delays in m(2)R-I(KACh) deactivation kinetics in both neonatal atrial myocytes and adult sinoatrial nodal cells. Rgs6(-/-) mice exhibited mild resting bradycardia and altered heart rate responses to pharmacological manipulations that were consistent with enhanced m(2)R-I(KACh) signaling. CONCLUSIONS: The cardiac Rgs6/Gbeta5 complex modulates the timing of parasympathetic influence on atrial myocytes and heart rate in mice. |
