Paper Info
Title
Hcn And Scn5a Channel Mutations: Implications For Impaired Atrioventricular Nodal Conduction In A Heterogeneous Computer Model Of The Whole Mouse Heart
Abstract
The atrioventricular (AV) node is a specialised region of the cardiac conduction system, allowing electrical excitation to propagate from the atria to the ventricles. AV block occurs when the AV node prevents electrical excitation waves reaching the ventricles, ultimately leading to a decrease in cardiac output. HCN4 and SCN5A defects have been associated with AV block, but the mechanisms underlying impaired AV node conduction remain incompletely understood.In this study we constructed a one-dimensional model for the mouse whole heart featuring detailed single cell models for sino-atrial node, atrium, ventricle and the AV node. The functional effects of HCN4 knock-out and the D1595N (SCN5A) mutation were simulated by modifying ion channel properties of I-f and I-Na respectively.Complete block of I-f in the model caused bradycardia; however, propagation was unaltered with no change in conduction velocity, suggesting the AV block caused by HCN4 knock-out is not a result of reduced I-f density. The D1595N mutation reduced conduction velocity throughout the model, leading to an increased PR interval (63ms vs. 43ms in control) indicative of 1(st) degree AV node block. The AV node exhibited reduced excitability which led to 2:1 block at a faster pacing rate.
Year
Venue
Keywords
2013
2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC)
genetics,molecular biophysics,proteins,cardiology,biochemistry
Field
DocType
Volume
Atrium (architecture),Mouse Heart,Internal medicine,Cardiology,Thermal conduction,NODAL,Cardiac output,Sinoventricular conduction,Physics,Electrical conduction system of the heart
Conference
40
ISSN
Citations 
PageRank 
2325-8861
0
0.34
References 
Authors
0
5
Name
Order
Citations
PageRank
simon j castro111.41
Michael A. Colman2146.92
Sanjay Kharche3104.21
Ruoxi Wang463.14
Henggui Zhang510551.88