Cardiovascular Research Advance Access first published online on September 30, 2008
This version [Corrected Proof] published online on October 22, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn266
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis
1 Department of Medicine, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec, Canada H1T 1C8
2 Department of Medicine, Université de Montréal, Quebec, Canada
3 Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany
* Corresponding author. Tel: +1 514 376 3330; fax: +1 514 593 2493. E-mail address: stanley.nattel{at}icm-mhi.org; stanleynattel{at}aol.com
Cardiac action potentials (APs) are driven by ionic currents flowing through specific channels and exchangers across cardiomyocyte membranes. Once initiated by rapid Na+ entry during phase 0, the AP time course is determined by the balance between inward depolarizing currents, carried mainly by Na+ and Ca2+, and outward repolarizing currents carried mainly by K+. K+ currents play a major role in repolarization. The loss of a K+ current can impair repolarization, but there is a redundancy of K+ currents so that when one K+ current is dysfunctional, other K+ currents increase to compensate, a phenomenon called ‘repolarization reserve’. Repolarization reserve protects repolarization under conditions that increase inward current or reduce outward current, threatening the balance that governs AP duration. This protection comes at the expense of reduced repolarization reserve, potentially resulting in unexpectedly large AP prolongation and arrhythmogenesis, when an additional repolarization-suppressing intervention is superimposed. The critical role of appropriate repolarization is such that cardiac rhythm stability can be impaired with either abnormally slow or excessively rapid repolarization. In cardiac disease states such as heart failure and atrial fibrillation (AF), changes in ion channel properties appear as part of an adaptive response to maintain function in the face of disease-related stress on the cardiovascular system. However, if the stress is maintained the adaptive ion channel changes may themselves lead to dysfunction, in particular cardiac arrhythmias. The present article reviews ionic remodelling of cardiac repolarization, and focuses on how potentially adaptive repolarization changes with congestive heart failure and AF can have arrhythmogenic consequences.
KEYWORDS Ion channels; Remodelling; Arrhythmia (mechanisms); Repolarization; Ventricular arrhythmias; Long QT syndrome; Membrane currents
Time for primary review: 20 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Nattel Calcium-activated potassium current: a novel ion channel candidate in atrial fibrillation J. Physiol., April 1, 2009; 587(7): 1385 - 1386. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Diez and G. Ertl A translational approach to myocardial remodelling Cardiovasc Res, February 15, 2009; 81(3): 409 - 411. [Full Text] [PDF]
|
|