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IKs Computational Modeling to Enforce the Investigation of D242N, a KV7.1 LQTS Mutation

Bartolucci, C; Moreno, C; Oliveras, A; Muñoz, C; De La Cruz, A; Peraza, DA; Gimeno, JR; ... Valenzuela, C; + view all (2017) IKs Computational Modeling to Enforce the Investigation of D242N, a KV7.1 LQTS Mutation. In: Pickett, Christine and Corsi, Cristiana and Laguna, Pablo and MacLeod, Rob, (eds.) Proceedings of Computing in Cardiology 2017. (pp. pp. 1-4). Computing in Cardiology: Rennes, France. Green open access

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Abstract

A KCNQ1 mutation, D242N, was found in a pair of twins and characterized at the cellular level. To investigate whether and how the mutation causes the clinically observed lost adaptation to fast heart rate, we performed a computational study. Firstly, we identified a new I Ks model based on voltage clamp experimental data. Then we included this formulation in the human action potential model of O'Hara Rudy (ORd) and simulate d the effects of the mutation. We also included adrenergic stimulation to the action potential, since the basal adrenergic tone is likely to affect the influence of I Ks on QTc in vivo. Finally, we simulated the pseudo-ECG, taking into account the heterogeneity of the cardiac wall. At the basal rate (60bpm), the mutation had negligible effects for all cell types, whereas at the high rate (180bpm), with concomitant β-adrenergic stimulation (mimicking exercise conditions), the mutant AP failed to adapt its duration to the same extent as the wild-type AP (e.g. 281ms vs. 267ms in M cells), due to a smaller amount of I Ks current. Pseudo-ECG results show only a slight rate adaptation, and the simulated QTc was significantly prolonged from 387ms to 493ms, similar to experimental recordings.

Type: Proceedings paper
Title: IKs Computational Modeling to Enforce the Investigation of D242N, a KV7.1 LQTS Mutation
Event: Computing in Cardiology 2017
Open access status: An open access version is available from UCL Discovery
DOI: 10.22489/CinC.2017.064-312
Publisher version: http://www.cinc.org/archives/2017/pdf/064-312.pdf
Language: English
Additional information: Published by Computing in Cardiology, 2017. http://www.cinc.org/ Articles in this volume are copyright (C) 2017 by their respective authors, and are licensed by their authors under the Creative Commons Attribution License 2.5 (CCAL). For the full text of the CCAL, please visit: http://creativecommons.org/licenses/by/2.5/
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 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
URI: https://discovery.ucl.ac.uk/id/eprint/10049740
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