Cargando…

Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node

Neurotransmitters released from sympathetic and parasympathetic nerve terminals in the sinoatrial node (SAN) exert their effects via G-protein-coupled receptors. Integration of these different G-protein signals within pacemaker cells of the SAN is critical for proper regulation of heart rate and fun...

Descripción completa

Detalles Bibliográficos
Autores principales: Mighiu, Alexandra S., Heximer, Scott P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374348/
https://www.ncbi.nlm.nih.gov/pubmed/22707940
http://dx.doi.org/10.3389/fphys.2012.00204
_version_ 1782235633186504704
author Mighiu, Alexandra S.
Heximer, Scott P.
author_facet Mighiu, Alexandra S.
Heximer, Scott P.
author_sort Mighiu, Alexandra S.
collection PubMed
description Neurotransmitters released from sympathetic and parasympathetic nerve terminals in the sinoatrial node (SAN) exert their effects via G-protein-coupled receptors. Integration of these different G-protein signals within pacemaker cells of the SAN is critical for proper regulation of heart rate and function. For example, excessive parasympathetic signaling can be associated with sinus node dysfunction (SND) and supraventricular arrhythmias. Our previous work has shown that one member of the regulator of G-protein signaling (RGS) protein family, RGS4, is highly and selectively expressed in pacemaker cells of the SAN. Consistent with its role as an inhibitor of parasympathetic signaling, RGS4-knockout mice have reduced basal heart rates and enhanced negative chronotropic responses to parasympathetic agonists. Moreover, RGS4 appears to be an important part of SA nodal myocyte signaling pathways that mediate G-protein-coupled inwardly rectifying potassium channel (GIRK) channel activation/deactivation and desensitization. Since RGS4 acts immediately downstream of M2 muscarinic receptors, it is tempting to speculate that RGS4 functions as a master regulator of parasympathetic signaling upstream of GIRKs, HCNs, and L-type Ca(2+) channels in the SAN. Thus, loss of RGS4 function may lead to increased susceptibility to conditions associated with increased parasympathetic signaling, including bradyarrhythmia, SND, and atrial fibrillation.
format Online
Article
Text
id pubmed-3374348
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Frontiers Research Foundation
record_format MEDLINE/PubMed
spelling pubmed-33743482012-06-15 Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node Mighiu, Alexandra S. Heximer, Scott P. Front Physiol Physiology Neurotransmitters released from sympathetic and parasympathetic nerve terminals in the sinoatrial node (SAN) exert their effects via G-protein-coupled receptors. Integration of these different G-protein signals within pacemaker cells of the SAN is critical for proper regulation of heart rate and function. For example, excessive parasympathetic signaling can be associated with sinus node dysfunction (SND) and supraventricular arrhythmias. Our previous work has shown that one member of the regulator of G-protein signaling (RGS) protein family, RGS4, is highly and selectively expressed in pacemaker cells of the SAN. Consistent with its role as an inhibitor of parasympathetic signaling, RGS4-knockout mice have reduced basal heart rates and enhanced negative chronotropic responses to parasympathetic agonists. Moreover, RGS4 appears to be an important part of SA nodal myocyte signaling pathways that mediate G-protein-coupled inwardly rectifying potassium channel (GIRK) channel activation/deactivation and desensitization. Since RGS4 acts immediately downstream of M2 muscarinic receptors, it is tempting to speculate that RGS4 functions as a master regulator of parasympathetic signaling upstream of GIRKs, HCNs, and L-type Ca(2+) channels in the SAN. Thus, loss of RGS4 function may lead to increased susceptibility to conditions associated with increased parasympathetic signaling, including bradyarrhythmia, SND, and atrial fibrillation. Frontiers Research Foundation 2012-06-13 /pmc/articles/PMC3374348/ /pubmed/22707940 http://dx.doi.org/10.3389/fphys.2012.00204 Text en Copyright © 2012 Mighiu and Heximer. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Physiology
Mighiu, Alexandra S.
Heximer, Scott P.
Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node
title Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node
title_full Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node
title_fullStr Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node
title_full_unstemmed Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node
title_short Controlling Parasympathetic Regulation of Heart Rate: A Gatekeeper Role for RGS Proteins in the Sinoatrial Node
title_sort controlling parasympathetic regulation of heart rate: a gatekeeper role for rgs proteins in the sinoatrial node
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374348/
https://www.ncbi.nlm.nih.gov/pubmed/22707940
http://dx.doi.org/10.3389/fphys.2012.00204
work_keys_str_mv AT mighiualexandras controllingparasympatheticregulationofheartrateagatekeeperroleforrgsproteinsinthesinoatrialnode
AT heximerscottp controllingparasympatheticregulationofheartrateagatekeeperroleforrgsproteinsinthesinoatrialnode