Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring

Abstract In adult mammalian hearts, atrioventricular rings (AVRs) surround the atrial orifices of atrioventricular valves and are hotbed of ectopic activity in patients with focal atrial tachycardia. Experimental data offering mechanistic insights into initiation and maintenance of ectopic foci is l...

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Autores principales:	Sunil Jit R. J. Logantha, Sanjay R. Kharche, Yu Zhang, Andrew J. Atkinson, Guoliang Hao, Mark R. Boyett, Halina Dobrzynski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/528dfa53538c4e9eb2e94d8b77e5e113
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spelling	oai:doaj.org-article:528dfa53538c4e9eb2e94d8b77e5e1132021-12-02T16:07:52ZSinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring10.1038/s41598-019-48276-02045-2322https://doaj.org/article/528dfa53538c4e9eb2e94d8b77e5e1132019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48276-0https://doaj.org/toc/2045-2322Abstract In adult mammalian hearts, atrioventricular rings (AVRs) surround the atrial orifices of atrioventricular valves and are hotbed of ectopic activity in patients with focal atrial tachycardia. Experimental data offering mechanistic insights into initiation and maintenance of ectopic foci is lacking. We aimed to characterise AVRs in structurally normal rat hearts, identify arrhythmia predisposition and investigate mechanisms underlying arrhythmogenicity. Extracellular potential mapping and intracellular action potential recording techniques were used for electrophysiology, qPCR for gene and, Western blot and immunohistochemistry for protein expression. Conditions favouring ectopic foci were assessed by simulations. In right atrial preparations, sinus node (SN) was dominant and AVRs displayed 1:1 impulse conduction. Detaching SN unmasked ectopic pacemaking in AVRs and pacemaker action potentials were SN-like. Blocking pacemaker current I f, and disrupting intracellular Ca2+ release, prolonged spontaneous cycle length in AVRs, indicating a role for SN-like pacemaker mechanisms. AVRs labelled positive for HCN4, and SERCA2a was comparable to SN. Pacemaking was potentiated by isoproterenol and abolished with carbachol and AVRs had abundant sympathetic nerve endings. β2-adrenergic and M2-muscarinic receptor mRNA and β2-receptor protein were comparable to SN. In computer simulations of a sick SN, ectopic foci in AVR were unmasked, causing transient suppression of SN pacemaking.Sunil Jit R. J. LoganthaSanjay R. KharcheYu ZhangAndrew J. AtkinsonGuoliang HaoMark R. BoyettHalina DobrzynskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-16 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sunil Jit R. J. Logantha Sanjay R. Kharche Yu Zhang Andrew J. Atkinson Guoliang Hao Mark R. Boyett Halina Dobrzynski Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
description	Abstract In adult mammalian hearts, atrioventricular rings (AVRs) surround the atrial orifices of atrioventricular valves and are hotbed of ectopic activity in patients with focal atrial tachycardia. Experimental data offering mechanistic insights into initiation and maintenance of ectopic foci is lacking. We aimed to characterise AVRs in structurally normal rat hearts, identify arrhythmia predisposition and investigate mechanisms underlying arrhythmogenicity. Extracellular potential mapping and intracellular action potential recording techniques were used for electrophysiology, qPCR for gene and, Western blot and immunohistochemistry for protein expression. Conditions favouring ectopic foci were assessed by simulations. In right atrial preparations, sinus node (SN) was dominant and AVRs displayed 1:1 impulse conduction. Detaching SN unmasked ectopic pacemaking in AVRs and pacemaker action potentials were SN-like. Blocking pacemaker current I f, and disrupting intracellular Ca2+ release, prolonged spontaneous cycle length in AVRs, indicating a role for SN-like pacemaker mechanisms. AVRs labelled positive for HCN4, and SERCA2a was comparable to SN. Pacemaking was potentiated by isoproterenol and abolished with carbachol and AVRs had abundant sympathetic nerve endings. β2-adrenergic and M2-muscarinic receptor mRNA and β2-receptor protein were comparable to SN. In computer simulations of a sick SN, ectopic foci in AVR were unmasked, causing transient suppression of SN pacemaking.
format	article
author	Sunil Jit R. J. Logantha Sanjay R. Kharche Yu Zhang Andrew J. Atkinson Guoliang Hao Mark R. Boyett Halina Dobrzynski
author_facet	Sunil Jit R. J. Logantha Sanjay R. Kharche Yu Zhang Andrew J. Atkinson Guoliang Hao Mark R. Boyett Halina Dobrzynski
author_sort	Sunil Jit R. J. Logantha
title	Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
title_short	Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
title_full	Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
title_fullStr	Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
title_full_unstemmed	Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
title_sort	sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/528dfa53538c4e9eb2e94d8b77e5e113
work_keys_str_mv	AT suniljitrjlogantha sinusnodelikepacemakermechanismsregulateectopicpacemakeractivityintheadultratatrioventricularring AT sanjayrkharche sinusnodelikepacemakermechanismsregulateectopicpacemakeractivityintheadultratatrioventricularring AT yuzhang sinusnodelikepacemakermechanismsregulateectopicpacemakeractivityintheadultratatrioventricularring AT andrewjatkinson sinusnodelikepacemakermechanismsregulateectopicpacemakeractivityintheadultratatrioventricularring AT guolianghao sinusnodelikepacemakermechanismsregulateectopicpacemakeractivityintheadultratatrioventricularring AT markrboyett sinusnodelikepacemakermechanismsregulateectopicpacemakeractivityintheadultratatrioventricularring AT halinadobrzynski sinusnodelikepacemakermechanismsregulateectopicpacemakeractivityintheadultratatrioventricularring
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Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring

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