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The involvement of TRPC3 channels in sinoatrial arrhythmias

Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity and mortality. The currently available treatments are limited and AF continues to be a major clinical challenge. Clinical studies have shown that AF is frequently associated with dysfunction in the sino-atrial node (SA...

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Autores principales: Ju, Yue-Kun, Lee, Bon Hyang, Trajanovska, Sofie, Hao, Gouliang, Allen, David G., Lei, Ming, Cannell, Mark B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373262/
https://www.ncbi.nlm.nih.gov/pubmed/25859221
http://dx.doi.org/10.3389/fphys.2015.00086
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author Ju, Yue-Kun
Lee, Bon Hyang
Trajanovska, Sofie
Hao, Gouliang
Allen, David G.
Lei, Ming
Cannell, Mark B.
author_facet Ju, Yue-Kun
Lee, Bon Hyang
Trajanovska, Sofie
Hao, Gouliang
Allen, David G.
Lei, Ming
Cannell, Mark B.
author_sort Ju, Yue-Kun
collection PubMed
description Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity and mortality. The currently available treatments are limited and AF continues to be a major clinical challenge. Clinical studies have shown that AF is frequently associated with dysfunction in the sino-atrial node (SAN). The association between AF and SAN dysfunction is probably related to the communication between the SAN and the surrounding atrial cells that form the SAN-atrial pacemaker complex and/or pathological processes that affect both the SAN and atrial simultaneously. Recent evidence suggests that Ca(2+) entry through TRPC3 (Transient Receptor Potential Canonical-3) channels may underlie several pathophysiological conditions -including cardiac arrhythmias. However, it is still not known if atrial and sinoatrial node cells are also involved. In this article we will first briefly review TRPC3 and IP(3)R signaling that relate to store/receptor-operated Ca(2+) entry (SOCE/ROCE) mechanisms and cardiac arrhythmias. We will then present some of our recent research progress in this field. Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3(−/−) mice) compared to wild type controls. We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP(3)R. Activation of G-protein coupled receptors (GPCRs) signaling that is able to modulate SOCE/ROCE and Ang II induced Ca(2+) homeostasis changes in sinoatrial complex being linked to TRPC3. The results provide new evidence that TRPC3 may play a role in sinoatrial and atrial arrhythmias that are caused by GPCRs activation.
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spelling pubmed-43732622015-04-09 The involvement of TRPC3 channels in sinoatrial arrhythmias Ju, Yue-Kun Lee, Bon Hyang Trajanovska, Sofie Hao, Gouliang Allen, David G. Lei, Ming Cannell, Mark B. Front Physiol Physiology Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity and mortality. The currently available treatments are limited and AF continues to be a major clinical challenge. Clinical studies have shown that AF is frequently associated with dysfunction in the sino-atrial node (SAN). The association between AF and SAN dysfunction is probably related to the communication between the SAN and the surrounding atrial cells that form the SAN-atrial pacemaker complex and/or pathological processes that affect both the SAN and atrial simultaneously. Recent evidence suggests that Ca(2+) entry through TRPC3 (Transient Receptor Potential Canonical-3) channels may underlie several pathophysiological conditions -including cardiac arrhythmias. However, it is still not known if atrial and sinoatrial node cells are also involved. In this article we will first briefly review TRPC3 and IP(3)R signaling that relate to store/receptor-operated Ca(2+) entry (SOCE/ROCE) mechanisms and cardiac arrhythmias. We will then present some of our recent research progress in this field. Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3(−/−) mice) compared to wild type controls. We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP(3)R. Activation of G-protein coupled receptors (GPCRs) signaling that is able to modulate SOCE/ROCE and Ang II induced Ca(2+) homeostasis changes in sinoatrial complex being linked to TRPC3. The results provide new evidence that TRPC3 may play a role in sinoatrial and atrial arrhythmias that are caused by GPCRs activation. Frontiers Media S.A. 2015-03-25 /pmc/articles/PMC4373262/ /pubmed/25859221 http://dx.doi.org/10.3389/fphys.2015.00086 Text en Copyright © 2015 Ju, Lee, Trajanovska, Hao, Allen, Lei and Cannell. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Ju, Yue-Kun
Lee, Bon Hyang
Trajanovska, Sofie
Hao, Gouliang
Allen, David G.
Lei, Ming
Cannell, Mark B.
The involvement of TRPC3 channels in sinoatrial arrhythmias
title The involvement of TRPC3 channels in sinoatrial arrhythmias
title_full The involvement of TRPC3 channels in sinoatrial arrhythmias
title_fullStr The involvement of TRPC3 channels in sinoatrial arrhythmias
title_full_unstemmed The involvement of TRPC3 channels in sinoatrial arrhythmias
title_short The involvement of TRPC3 channels in sinoatrial arrhythmias
title_sort involvement of trpc3 channels in sinoatrial arrhythmias
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373262/
https://www.ncbi.nlm.nih.gov/pubmed/25859221
http://dx.doi.org/10.3389/fphys.2015.00086
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