Pulmonary vein sleeve cell excitation-contraction-coupling becomes dysynchronized by spontaneous calcium transients

TY - JOUR

T1 - Pulmonary vein sleeve cell excitation-contraction-coupling becomes dysynchronized by spontaneous calcium transients

AU - Rietdorf, Katja

AU - Masoud, Said

AU - McDonald, Fraser

AU - Sanderson, Michael J.

AU - Bootman, Martin D.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.

AB - Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. Substantial evidence indicates that cardiomyocytes located in the pulmonary veins [pulmonary vein sleeve cells (PVCs)] cause AF by generating ectopic electrical activity. Electrical ablation, isolating PVCs from their left atrial junctions, is a major treatment for AF. In small rodents, the sleeve of PVCs extends deep inside the lungs and is present in lung slices. Here we present data, using the lung slice preparation, characterizing how spontaneous Ca2+ transients in PVCs affect their capability to respond to electrical pacing. Immediately after a spontaneous Ca2+ transient the cell is in a refractory period and it cannot respond to electrical stimulation. Consequently, we observe that the higher the level of spontaneous activity in an individual PVC, the less likely it is that this PVC responds to electrical field stimulation. The spontaneous activity of neighbouring PVCs can be different from each other. Heterogeneity in the Ca2+ signalling of cells and in their responsiveness to electrical stimuli are known pro-arrhythmic events. The tendency of PVCs to show spontaneous Ca2+ transients and spontaneous action potentials (APs) underlies their potential to cause AF.

KW - Atrial fibrillation

KW - Calcium signalling

KW - Cardiac arrhythmia

KW - Lung slice

KW - Pulmonary vein myocyte

UR - http://www.scopus.com/inward/record.url?scp=84935029206&partnerID=8YFLogxK

U2 - 10.1042/BST20140299

DO - 10.1042/BST20140299

M3 - Article

AN - SCOPUS:84935029206

SN - 0300-5127

VL - 43

SP - 410

EP - 416

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

ER -