In mouse pulmonary vein sleeve cells, inherent spontaneous calcium activity disrupted electrical pacing, with higher frequencies of spontaneous activity (>1.5 Hz) rendering pacing less effective.
Heterogeneous spontaneous Ca(2+) activity in pulmonary vein sleeve cells can disrupt electrical pacing, providing a cellular mechanism for autonomous, pro-arrhythmic activity that may lead to atrial fibrillation.
The pulmonary vein, which returns oxygenated blood to the left atrium, is ensheathed by a population of unique, myocyte-like cells called pulmonary vein sleeve cells (PVCs). These cells autonomously generate action potentials that propagate into the left atrial chamber and cause arrhythmias resulting in atrial fibrillation; the most common, often sustained, form of cardiac arrhythmia. In mice, PVCs extend along the pulmonary vein into the lungs, and are accessible in a lung slice preparation. We exploited this model to study how aberrant Ca(2+) signaling alters the ability of PVC networks to follow electrical pacing. Cellular responses were investigated using real-time 2-photon imaging of lung slices loaded with a Ca(2+)-sensitive fluorescent indicator (Ca(2+) measurements) and phase contrast microscopy (contraction measurements). PVCs displayed global Ca(2+) signals and coordinated contraction in response to electrical field stimulation (EFS). The effects of EFS relied on both Ca(2+) influx and Ca(2+) release, and could be inhibited by nifedipine, ryanodine or caffeine. Moreover, PVCs had a high propensity to show spontaneous Ca(2+) signals that arose via stochastic activation of ryanodine receptors (RyRs). The ability of electrical pacing to entrain Ca(2+) signals and contractile responses was dramatically influenced by inherent spontaneous Ca(2+) activity. In PVCs with relatively low spontaneous Ca(2+) activity (1.5 Hz), electrical pacing was less effective; PVCs became unpaced, only partially-paced or displayed alternans. Because spontaneous Ca(2+) activity varied between cells, neighboring PVCs often had different responses to electrical pacing. Our data indicate that the ability of PVCs to respond to electrical stimulation depends on their intrinsic Ca(2+) cycling properties. Heterogeneous spontaneous Ca(2+) activity arising from stochastic RyR opening can disengage them from sinus rhythm and lead to autonomous, pro-arrhythmic activity.
Rietdorf et al. (Thu,) conducted a other in Atrial Fibrillation (preclinical model). Electrical field stimulation (EFS) vs. Baseline spontaneous activity was evaluated on Entrainment of Ca2+ signals and contractile responses. In mouse pulmonary vein sleeve cells, inherent spontaneous calcium activity disrupted electrical pacing, with higher frequencies of spontaneous activity (>1.5 Hz) rendering pacing less effective.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: