Na/K pump regulation of cardiac repolarization: insights from a systems biology approach

Handle URI:
http://hdl.handle.net/10754/598929
Title:
Na/K pump regulation of cardiac repolarization: insights from a systems biology approach
Authors:
Bueno-Orovio, Alfonso; Sánchez, Carlos; Pueyo, Esther; Rodriguez, Blanca
Abstract:
The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies. © 2013 Springer-Verlag Berlin Heidelberg.
Citation:
Bueno-Orovio A, Sánchez C, Pueyo E, Rodriguez B (2013) Na/K pump regulation of cardiac repolarization: insights from a systems biology approach. Pflugers Arch - Eur J Physiol 466: 183–193. Available: http://dx.doi.org/10.1007/s00424-013-1293-1.
Publisher:
Springer Nature
Journal:
Pflügers Archiv - European Journal of Physiology
KAUST Grant Number:
KUK-C1-013-04
Issue Date:
15-May-2013
DOI:
10.1007/s00424-013-1293-1
PubMed ID:
23674099
Type:
Article
ISSN:
0031-6768; 1432-2013
Sponsors:
The first author's contribution to this work was supported by Award no. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST). CS and EP are supported by grant TEC2010-19410 from Ministerio de Economia y Competitividad (MINECO), Spain. EP acknowledges the financial support of Ramon y Cajal program from MINECO, Spain. BR holds Medical Research Council Career Development, Industrial Partnership and MRC Centenary Awards.
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Full metadata record

DC FieldValue Language
dc.contributor.authorBueno-Orovio, Alfonsoen
dc.contributor.authorSánchez, Carlosen
dc.contributor.authorPueyo, Estheren
dc.contributor.authorRodriguez, Blancaen
dc.date.accessioned2016-02-25T13:43:55Zen
dc.date.available2016-02-25T13:43:55Zen
dc.date.issued2013-05-15en
dc.identifier.citationBueno-Orovio A, Sánchez C, Pueyo E, Rodriguez B (2013) Na/K pump regulation of cardiac repolarization: insights from a systems biology approach. Pflugers Arch - Eur J Physiol 466: 183–193. Available: http://dx.doi.org/10.1007/s00424-013-1293-1.en
dc.identifier.issn0031-6768en
dc.identifier.issn1432-2013en
dc.identifier.pmid23674099en
dc.identifier.doi10.1007/s00424-013-1293-1en
dc.identifier.urihttp://hdl.handle.net/10754/598929en
dc.description.abstractThe sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies. © 2013 Springer-Verlag Berlin Heidelberg.en
dc.description.sponsorshipThe first author's contribution to this work was supported by Award no. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST). CS and EP are supported by grant TEC2010-19410 from Ministerio de Economia y Competitividad (MINECO), Spain. EP acknowledges the financial support of Ramon y Cajal program from MINECO, Spain. BR holds Medical Research Council Career Development, Industrial Partnership and MRC Centenary Awards.en
dc.publisherSpringer Natureen
dc.subjectCardiac repolarizationen
dc.subjectModelingen
dc.subjectSodium-potassium pumpen
dc.subjectSystems biologyen
dc.titleNa/K pump regulation of cardiac repolarization: insights from a systems biology approachen
dc.typeArticleen
dc.identifier.journalPflügers Archiv - European Journal of Physiologyen
dc.contributor.institutionUniversity of Oxford, Oxford, United Kingdomen
dc.contributor.institutionUniversidad de Zaragoza, Zaragoza, Spainen
dc.contributor.institutionBiomedical Research Networking Center in Bioengineering, Zaragoza, Spainen
kaust.grant.numberKUK-C1-013-04en
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