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.
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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.
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