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Control of ventricular excitability by neurons of the dorsal motor nucleus of the vagus nerve

Machhada, Asif, Ang, Richard, Ackland, Gareth L., Ninkina, Natalia, Buchman, Vladimir L., Lythgoe, Mark F., Trapp, Stefan, Tinker, Andrew, Marina, Nephtali and Gourine, Alexander V. 2015. Control of ventricular excitability by neurons of the dorsal motor nucleus of the vagus nerve. Heart Rhythm 12 (11) , pp. 2285-2293. 10.1016/j.hrthm.2015.06.005

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Abstract

Background The central nervous origins of functional parasympathetic innervation of cardiac ventricles remain controversial. Objective This study aimed to identify a population of vagal preganglionic neurons that contribute to the control of ventricular excitability. An animal model of synuclein pathology relevant to Parkinson’s disease was used to determine whether age-related loss of the activity of the identified group of neurons is associated with changes in ventricular electrophysiology. Methods In vivo cardiac electrophysiology was performed in anesthetized rats in conditions of selective inhibition of the dorsal vagal motor nucleus (DVMN) neurons by pharmacogenetic approach and in mice with global genetic deletion of all family members of the synuclein protein. Results In rats anesthetized with urethane (in conditions of systemic beta-adrenoceptor blockade), muscarinic and neuronal nitric oxide synthase blockade confirmed the existence of a tonic parasympathetic control of cardiac excitability mediated by the actions of acetylcholine and nitric oxide. Acute DVMN silencing led to shortening of the ventricular effective refractory period (vERP), a lowering of the threshold for triggered ventricular tachycardia, and prolongation of the corrected QT (QTc) interval. Lower resting activity of the DVMN neurons in aging synuclein-deficient mice was found to be associated with vERP shortening and QTc interval prolongation. Conclusion Activity of the DVMN vagal preganglionic neurons is responsible for tonic parasympathetic control of ventricular excitability, likely to be mediated by nitric oxide. These findings provide the first insight into the central nervous substrate that underlies functional parasympathetic innervation of the ventricles and highlight its vulnerability in neurodegenerative diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: Available online 5 June 2015
Publisher: Elsevier
ISSN: 1547-5271
Date of First Compliant Deposit: 14 March 2019
Last Modified: 30 Mar 2020 15:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/85750

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