Arrhythmogenic ionic remodeling: adaptive responses with maladaptive consequences.
Compensatory changes in ion transport mechanisms occur in response to a variety of cardiac disease processes. Recent work has demonstrated that these adaptive responses can produce the arrhythmogenic substrate for a variety of important cardiac rhythm disorders. Two important paradigms are atrial tachycardia-induced remodeling and ionic remodeling caused by congestive heart failure. Atrial tachycardia promotes cellular Ca(2)+ loading and downregulates a variety of ion channels, particularly L-type Ca(2)+ channels, thereby promoting the occurrence and maintenance of atrial fibrillation. Congestive heart failure alters the expression and function of a variety of membrane transport processes, including several K(+)-channels and key Ca(2)+-transport systems, favoring the occurrence of arrhythmogenic afterdepolarizations. An improved understanding of the mechanisms and consequences of arrhythmogenic ionic remodeling promises to lead to novel and improved therapeutic approaches.
Nattel
S
S
Department of Medicine and Research Center, Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada. nattel@icm.umontreal.ca
Khairy
P
P
Schram
G
G
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism*; D004285:Dogs; D006333:Heart Failure / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013610:Tachycardia / Q000150:complications* / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology*