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Autonomic modulation of the electrical substrate in mice haploinsufficient for cardiac sodium channels: a model of the Brugada syndrome

Finlay, M; Bhar-Amato, J; Ng, K-E; Santos, D; Orini, M; Vyas, V; Taggart, P; ... Tinker, A; + view all (2019) Autonomic modulation of the electrical substrate in mice haploinsufficient for cardiac sodium channels: a model of the Brugada syndrome. American Journal of Physiology: Cell Physiology , 317 (3) C576-C583. 10.1152/ajpcell.00028.2019. Green open access

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Abstract

A murine line with a haploinsufficiency in SCN5A has been used to model human Brugada syndrome: a disease causing sudden cardiac death due to lethal ventricular arrhythmias. We explored the effects of cholinergic tone on electrophysiological parameters in wild type and genetically modified, heterozygous, Scn5a+/- knockout mice. Scn5a+/-, ventricular slices showed longer refractory periods than wild-type both at baseline (Scn5a+/- 79±4 vs WT 63±4 ms, p <0.001) and during isoprenaline challenge. Scn5a+/- hearts also showed lower conduction velocities than did WT at baseline (0.27±0.04 vs 0.47±0.11 m/s, p=0.01) and blunted responses to isoprenaline challenge. Carbachol exerted limited effects but reversed the effects of isoprenaline with co-application. Scn5a+/- mice showed a reduction in conduction reserve in that isoprenaline no longer increased conduction velocity and this was not antagonised by muscarinic agonists.

Type: Article
Title: Autonomic modulation of the electrical substrate in mice haploinsufficient for cardiac sodium channels: a model of the Brugada syndrome
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1152/ajpcell.00028.2019
Publisher version: https://doi.org/10.1152/ajpcell.00028.2019
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Autonomic nervous system, Brugada syndrome, Scn5A, conduction
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
URI: https://discovery.ucl.ac.uk/id/eprint/10080620
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