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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bueno-Orovio, Alfonso Sánchez, Carlos Pueyo, Esther Rodriguez, Blanca
Description	Author Affiliation: Bueno-Orovio A ( Department of Computer Science, University of Oxford, Wolfson Building, Parks Road, Oxford, OX1 3QD, UK, alfonso.bueno@cs.ox.ac.uk.)
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.
File Format	HTM / HTML
ISSN	00316768
Issue Number	2
Volume Number	466
e-ISSN	14322013
Journal	Pflügers Archiv - European Journal of Physiology
Language	English
Publisher	Springer
Publisher Date	2014-02-01
Publisher Place	Germany
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Physiology Action Potentials Physiology Calcium Metabolism Heart Myocardium Potassium Sodium-potassium-exchanging Atpase Sodium Drug Effects Animals Cardiac Glycosides Pharmacology Computer Simulation Humans Ion Transport Systems Biology Journal Article Research Support, Non-u.s. Gov't Review
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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