Potential role of regulator of G-protein signaling 5 in the protection of Vagal-related bradycardia and atrial tachyarrhythmia

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 ikach 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 (ikach) 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 ikach current. © 2016 the authors.