Potential Role of Regulator of G‐Protein Signaling 5 in the Protection of Vagal‐Related Bradycardia and Atrial Tachyarrhythmia. Issue 3 (9th March 2016)

• Record Type: Journal Article
• Authors: Qin, Mu; Liu, Xu; Liu, Tao; Wang, Teng; Huang, Congxin
• Is Part Of: Journal of the American Heart Association. Volume 5:Issue 3(2016)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-03-09
• Subjects: atrial tachyarrhythmia -- bradycardia -- IKAch -- regulator of G‐protein signaling 5; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.115.002783
• Languages: English
• ISSNs: 2047-9980

Abstract

Abstract : Background: The regulator of G‐protein signaling 5 (Rgs5), which functions as the regulator of G‐protein‐coupled receptor (GPCR) including muscarinic receptors, has a potential effect on atrial muscarinic receptor‐activated IKA ch current. Methods and Results: In the present study, hearts of Rgs5 knockout (KO) mice had decreased low‐frequency/high‐frequency ratio in spectral measures of heart rate variability. Loss of Rgs5 provoked dramatically exaggerated bradycardia and significantly ( P <0.05) prolonged sinus nodal recovery time in response to carbachol (0.1 mg/kg, intraperitoneally). Compared to those from wild‐type (WT) mice, Langendorff perfused hearts from Rgs5 KO mice had significantly ( P <0.01) abbreviated atrial effective refractory periods and increased dominant frequency after administration of acetylcholine (ACh; 1 μmol/L). In addition, whole patch clamp analyses of single atrial myocytes revealed that the ACh‐regulated potassium current (IKA ch ) was significant increased in the time course of activation and deactivation ( P <0.01) in Rgs5 KO, compared to those in WT, mice. To further determine the effect of Rgs5, transgenic mice with cardiac‐specific overexpression of human Rgs5 were found to be resistant to ACh‐related effects in bradycardia, atrial electrophysiology, and atrial tachyarrhythmia (AT). Conclusion: The results of this study indicate that, as a critical regulator of parasympathetic activation in the heart, Rgs5 prevents vagal‐related bradycardia and AT through negatively regulating the IKA ch current.