title: Potential Role of Regulator of G-Protein Signaling 5 in the Protection of Vagal-Related Bradycardia and Atrial Tachyarrhythmia.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China huangcongxing1951@126.com qinmu-1001@live.cn.
authors.forename: Mu
authors.initials: M
authors.lastname: Qin
authors.affiliation: Department of Cardiology, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Institute of Wuhan University, Wuhan, China huangcongxing1951@126.com qinmu-1001@live.cn.
authors.forename: Congxin
authors.initials: C
authors.lastname: Huang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001919:Bradycardia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002217:Carbachol; D018679:Cholinergic Agonists / Q000494:pharmacology; D004195:Disease Models, Animal; D006321:Heart / Q000294:innervation*; D006339:Heart Rate; D006801:Humans; D000067268:Isolated Heart Preparation; D008297:Male; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D020710:RGS Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D012032:Refractory Period, Electrophysiological; D013617:Tachycardia, Supraventricular / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D014630:Vagus Nerve / Q000503:physiopathology*
chemical_list: D018679:Cholinergic Agonists; D020710:RGS Proteins; C491349:RGS5 protein, human; D011976:Receptors, Muscarinic; C105346:Rgs5 protein, mouse; D002217:Carbachol; D000109:Acetylcholine; D011188:Potassium
keywords: IKAch; atrial tachyarrhythmia; bradycardia; regulator of G‐protein signaling 5