English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/189692
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


IKs computational modeling to enforce the investigation of D242N, a Kv7.1 LQTS mutation

AuthorsBartolucci, Chiara; Moreno, Cristina; Oliveras, Anna; Muñoz, Carmen; Cruz, Alicia de la ; Peraza, Diego A.; Gimeno, Juan R.; Martín-Martínez, Mercedes ; Severi, Stefano; Felipe, Antonio; Lambiase, Pier; González, Teresa ; Valenzuela, Carmen
Issue Date2017
CitationComputing in Cardiology Conference (2017)
AbstractA 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 simulated 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.
DescriptionTrabajo presentado a la Computing in Cardiology Conference, celebrada en Rennes (Francia) del 24 al 27 de septiembre de 2017.
Appears in Collections:(IIBM) Comunicaciones congresos
Files in This Item:
File Description SizeFormat 
IKsmutati.pdf835,95 kBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.