• Calcium signalling silencing in atrial fibrillation

      Greiser, M. (Blackwell Publishing Ltd, 2017)
      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+]i signal 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+]i transient, 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. Copyright 2017 The Authors. The Journal of Physiology Copyright 2017 The Physiological Society