<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Yang, Jianqi</style></author><author><style face="normal" font="default" size="100%">Huang, Jie</style></author><author><style face="normal" font="default" size="100%">Maity, Biswanath</style></author><author><style face="normal" font="default" size="100%">Gao, Zhan</style></author><author><style face="normal" font="default" size="100%">Lorca, Ramón A</style></author><author><style face="normal" font="default" size="100%">Gudmundsson, Hjalti</style></author><author><style face="normal" font="default" size="100%">Li, Jingdong</style></author><author><style face="normal" font="default" size="100%">Stewart, Adele</style></author><author><style face="normal" font="default" size="100%">Swaminathan, Paari Dominic</style></author><author><style face="normal" font="default" size="100%">Ibeawuchi, Stella-Rita</style></author><author><style face="normal" font="default" size="100%">Shepherd, Andrew</style></author><author><style face="normal" font="default" size="100%">Chen, Ching-Kang</style></author><author><style face="normal" font="default" size="100%">Kutschke, William</style></author><author><style face="normal" font="default" size="100%">Mohler, Peter J</style></author><author><style face="normal" font="default" size="100%">Mohapatra, Durga P</style></author><author><style face="normal" font="default" size="100%">Anderson, Mark E</style></author><author><style face="normal" font="default" size="100%">Fisher, Rory A</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">RGS6, a modulator of parasympathetic activation in heart.</style></title><secondary-title><style face="normal" font="default" size="100%">Circ Res</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Circ. Res.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Action Potentials</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Bradycardia</style></keyword><keyword><style  face="normal" font="default" size="100%">Cells, Cultured</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart</style></keyword><keyword><style  face="normal" font="default" size="100%">Heart Rate</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, 129 Strain</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Knockout</style></keyword><keyword><style  face="normal" font="default" size="100%">Parasympathetic Fibers, Postganglionic</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptor, Muscarinic M2</style></keyword><keyword><style  face="normal" font="default" size="100%">RGS Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Sinoatrial Node</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">11/2010</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">107</style></volume><pages><style face="normal" font="default" size="100%">1345-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;RATIONALE: &lt;/b&gt;Parasympathetic regulation of heart rate is mediated by acetylcholine binding to G protein-coupled muscarinic M2 receptors, which activate heterotrimeric G(i/o) proteins to promote G protein-coupled inwardly rectifying K(+) (GIRK) channel activation. Regulator of G protein signaling (RGS) proteins, which function to inactivate G proteins, are indispensable for normal parasympathetic control of the heart. However, it is unclear which of the more than 20 known RGS proteins function to negatively regulate and thereby ensure normal parasympathetic control of the heart.&lt;/p&gt;

&lt;p&gt;&lt;b&gt;OBJECTIVE: &lt;/b&gt;To examine the specific contribution of RGS6 as an essential regulator of parasympathetic signaling in heart.&lt;/p&gt;

&lt;p&gt;&lt;b&gt;METHODS AND RESULTS: &lt;/b&gt;We developed RGS6 knockout mice to determine the functional impact of loss of RGS6 on parasympathetic regulation of cardiac automaticity. RGS6 exhibited a uniquely robust expression in the heart, particularly in sinoatrial and atrioventricular nodal regions. Loss of RGS6 provoked dramatically exaggerated bradycardia in response to carbachol in mice and isolated perfused hearts and significantly enhanced the effect of carbachol on inhibition of spontaneous action potential firing in sinoatrial node cells. Consistent with a role of RGS6 in G protein inactivation, RGS6-deficient atrial myocytes exhibited a significant reduction in the time course of acetylcholine-activated potassium current (I(K)(ACh)) activation and deactivation, as well as the extent of I(K)(ACh) desensitization.&lt;/p&gt;

&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;RGS6 is a previously unrecognized, but essential, regulator of parasympathetic activation in heart, functioning to prevent parasympathetic override and severe bradycardia. These effects likely result from actions of RGS6 as a negative regulator of G protein activation of GIRK channels.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue><custom1><style face="normal" font="default" size="100%">&lt;p&gt;http://www.ncbi.nlm.nih.gov/pubmed/20864673?dopt=Abstract&lt;/p&gt;
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