TY - JOUR
T1 - Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation
AU - Lu, Yen Yu
AU - Chen, Yao Chang
AU - Kao, Yu Hsun
AU - Chen, Shih Ann
AU - Chen, Yi Jen
N1 - Publisher Copyright:
© 2013 Elsevier Ltd
PY - 2013/6/1
Y1 - 2013/6/1
N2 - Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10 μg/ml, 5–7 h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n = 25), collagen-treated PV cardiomyocytes (n = 22) had a faster beating rate (3.2 ± 04 vs. 1.9 ± 0.2 Hz, p < 0.005) and a larger amplitude of delayed afterdepolarization (16 ± 2 vs. 10 ± 1 mV, p < 0.01). Moreover, collagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca2 +-activated K+ current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF.
AB - Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10 μg/ml, 5–7 h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n = 25), collagen-treated PV cardiomyocytes (n = 22) had a faster beating rate (3.2 ± 04 vs. 1.9 ± 0.2 Hz, p < 0.005) and a larger amplitude of delayed afterdepolarization (16 ± 2 vs. 10 ± 1 mV, p < 0.01). Moreover, collagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca2 +-activated K+ current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF.
KW - Atrial fibrillation
KW - Collagen
KW - Pulmonary veins
KW - p38 MAPK
UR - http://www.scopus.com/inward/record.url?scp=84875943666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875943666&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2013.03.008
DO - 10.1016/j.yjmcc.2013.03.008
M3 - Article
C2 - 23524328
AN - SCOPUS:84875943666
SN - 0022-2828
VL - 59
SP - 159
EP - 166
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -