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 journalArticlepeer-review

23 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 (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.

Original languageEnglish
Pages (from-to)159-166
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume59
DOIs
Publication statusPublished - Jun 1 2013

Keywords

  • Atrial fibrillation
  • Collagen
  • Pulmonary veins
  • p38 MAPK

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation'. Together they form a unique fingerprint.

Cite this