title: Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis.
abstract: 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 Ca(2+), 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.
authors.affiliation: Department of Medicine, Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec, Canada H1T 1C8.
authors.forename: Georghia
authors.initials: G
authors.lastname: Michael
authors.forename: Ling
authors.initials: L
authors.lastname: Xiao
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Qi
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dobrev
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000200:Action Potentials; D000222:Adaptation, Physiological; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D001281:Atrial Fibrillation / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D015220:Calcium Channels / Q000378:metabolism; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D011379:Prognosis; D012084:Renin-Angiotensin System; D015222:Sodium Channels / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels