Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation

Yen Yu Lu, Yao Chang Chen, Yu Hsun Kao, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 (10μg/ml, 5-7h) 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±0.2Hz, p2+-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.

Original languageEnglish
Pages (from-to)159-166
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume59
DOIs
Publication statusAccepted/In press - Jun 2013

Fingerprint

Pulmonary Veins
p38 Mitogen-Activated Protein Kinases
Extracellular Matrix
Collagen
Cardiac Myocytes
Atrial Fibrillation
Action Potentials
Potassium
Sodium
Atrial Remodeling
Patch-Clamp Techniques
Cardiac Arrhythmias
Fibrosis
Phosphorylation
Rabbits
Calcium

Keywords

  • Atrial fibrillation
  • Collagen
  • P38 MAPK
  • Pulmonary veins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

Cite this

Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation. / Lu, Yen Yu; Chen, Yao Chang; Kao, Yu Hsun; Chen, Shih Ann; Chen, Yi Jen.

In: Journal of Molecular and Cellular Cardiology, Vol. 59, 06.2013, p. 159-166.

Research output: Contribution to journalArticle

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