Calcium signalling silencing in atrial fibrillation.
Subcellular calcium signalling silencing is a novel and distinct cellular and molecular adaptive response to rapid cardiac activation. Calcium signalling silencing develops during short-term sustained rapid atrial activation as seen clinically during paroxysmal atrial fibrillation (AF). It is the first 'anti-arrhythmic' adaptive response in the setting of AF and appears to counteract the maladaptive changes that lead to intracellular Ca2+signalling instability and Ca2+-based arrhythmogenicity. Calcium signalling silencing results in a failed propagation of the [Ca2+]isignal to the myocyte centre both in patients with AF and in a rabbit model. This adaptive mechanism leads to a substantial reduction in the expression levels of calcium release channels (ryanodine receptors, RyR2) in the sarcoplasmic reticulum, and the frequency of Ca2+sparks and arrhythmogenic Ca2+waves remains low. Less Ca2+release per [Ca2+]itransient, increased fast Ca2+buffering strength, shortened action potentials and reduced L-type Ca2+current contribute to a substantial reduction of intracellular [Na+]. These features of Ca2+signalling silencing are distinct and in contrast to the changes attributed to Ca2+-based arrhythmogenicity. Some features of Ca2+signalling silencing prevail in human AF suggesting that the Ca2+signalling 'phenotype' in AF is a sum of Ca2+stabilizing (Ca2+signalling silencing) and Ca2+destabilizing (arrhythmogenic unstable Ca2+signalling) factors. Calcium signalling silencing is a part of the mechanisms that contribute to the natural progression of AF and may limit the role of Ca2+-based arrhythmogenicity after the onset of AF.
Center for Biomedical Engineering and Technology and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Maura
0000-0002-3197-0910
M
Greiser
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium
atrial fibrillation; atrial myocyte; calcium dynamics; calcium imaging