[Electrical remodeling in atrial fibrillation--cellular and molecular mechanisms].
Atrial fibrillation is associated with changes in atrial electrophysiology that facilitate the initiation and persistence of the arrhythmia. The underlying cellular and molecular mechanisms are diverse; they have intensively been investigated over the past few years. The results, that have substantially improved the understanding of the pathophysiology of atrial fibrillation are reviewed. On the cellular level, atrial fibrillation leads to a strong shortening and an impaired rate adaptation of the action potential as well as changes in action potential morphology. Atrial fibrillation is associated with an altered gene expression of the L-type calcium channel (ICa,L) and of potassium channels (Ito, IK1, IKACh). The molecular mechanisms of intraatrial conduction slowing are less well understood; changes in the expression or distribution of gap junction proteins or a decrease of the fast sodium inward channel (INa) seem to be involved. A trigger for many of the observations is an overload of the myocyte cytoplasm with Ca2+ and a consecutive decrease of the systolic calcium gradient, furthermore changes in calcium-handling proteins are detectable in atrial fibrillation. In the last part, the clinical relevance and potential new therapeutic approaches are discussed.
Bosch
R F
RF
Medizinische Universitätsklinik Abteilung III, Tübingen. ralph.bosch@uni-tuebingen.de
Grammer
J B
JB
Kühlkamp
V
V
Seipel
L
L
D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology; D017630:Connexins / Q000235:genetics / Q000502:physiology; D004562:Electrocardiography; D015870:Gene Expression / Q000502:physiology; D006329:Heart Conduction System / Q000503:physiopathology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology
D017630:Connexins; D007473:Ion Channels; D002118:Calcium