Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation
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Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation. / Poulet, Claire; Künzel, Stephan; Büttner, Edgar; Lindner, Diana; Westermann, Dirk; Ravens, Ursula.
In: Physiol Rep, Vol. 4, No. 2, 02.2016.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation
AU - Poulet, Claire
AU - Künzel, Stephan
AU - Büttner, Edgar
AU - Lindner, Diana
AU - Westermann, Dirk
AU - Ravens, Ursula
N1 - © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
PY - 2016/2
Y1 - 2016/2
N2 - The contribution of human atrial fibroblasts to cardiac physiology and pathophysiology is poorly understood. Fibroblasts may contribute to arrhythmogenesis through fibrosis, or by directly altering electrical activity in cardiomyocytes. The objective of our study was to uncover phenotypic differences between cells from patients in sinus rhythm (SR) and chronic atrial fibrillation (AF), with special emphasis on electrophysiological properties. We isolated fibroblasts from human right atrial tissue for patch-clamp experiments, proliferation, migration, and differentiation assays, and gene expression profiling. In culture, proliferation and migration of AF fibroblasts were strongly impaired but differentiation into myofibroblasts was increased. This was associated with a higher number of AF fibroblasts expressing functional Nav1.5 channels. Strikingly Na(+) currents were considerably larger in AF cells. Blocking Na(+) channels in culture with tetrodotoxin did not affect proliferation, migration, or differentiation in neither SR nor AF cells. While freshly isolated fibroblasts showed mostly weak rectifier currents, fibroblasts in culture developed outward rectifier K(+) currents of similar amplitude between the SR and AF groups. Adding the K(+) channel blockers tetraethylammonium and 4-aminopyridin in culture reduced current amplitude and inhibited proliferation in the SR group only. Analysis of gene expression revealed significant differences between SR and AF in genes encoding for ion channels, collagen, growth factors, connexins, and cadherins. In conclusion, this study shows that under AF conditions atrial fibroblasts undergo phenotypic changes that are revealed in culture. Future experiments should be performed in situ to understand the nature of those changes and whether they affect cardiac electrical activity.
AB - The contribution of human atrial fibroblasts to cardiac physiology and pathophysiology is poorly understood. Fibroblasts may contribute to arrhythmogenesis through fibrosis, or by directly altering electrical activity in cardiomyocytes. The objective of our study was to uncover phenotypic differences between cells from patients in sinus rhythm (SR) and chronic atrial fibrillation (AF), with special emphasis on electrophysiological properties. We isolated fibroblasts from human right atrial tissue for patch-clamp experiments, proliferation, migration, and differentiation assays, and gene expression profiling. In culture, proliferation and migration of AF fibroblasts were strongly impaired but differentiation into myofibroblasts was increased. This was associated with a higher number of AF fibroblasts expressing functional Nav1.5 channels. Strikingly Na(+) currents were considerably larger in AF cells. Blocking Na(+) channels in culture with tetrodotoxin did not affect proliferation, migration, or differentiation in neither SR nor AF cells. While freshly isolated fibroblasts showed mostly weak rectifier currents, fibroblasts in culture developed outward rectifier K(+) currents of similar amplitude between the SR and AF groups. Adding the K(+) channel blockers tetraethylammonium and 4-aminopyridin in culture reduced current amplitude and inhibited proliferation in the SR group only. Analysis of gene expression revealed significant differences between SR and AF in genes encoding for ion channels, collagen, growth factors, connexins, and cadherins. In conclusion, this study shows that under AF conditions atrial fibroblasts undergo phenotypic changes that are revealed in culture. Future experiments should be performed in situ to understand the nature of those changes and whether they affect cardiac electrical activity.
KW - Aged
KW - Atrial Fibrillation/metabolism
KW - Cell Differentiation/physiology
KW - Cell Movement/physiology
KW - Cell Proliferation/physiology
KW - Cells, Cultured
KW - Chronic Disease
KW - Female
KW - Fibroblasts/metabolism
KW - Heart Atria/metabolism
KW - Humans
KW - Immunohistochemistry
KW - Ion Channels/metabolism
KW - Male
KW - Middle Aged
KW - Oligonucleotide Array Sequence Analysis
KW - Patch-Clamp Techniques
KW - Transcriptome
U2 - 10.14814/phy2.12681
DO - 10.14814/phy2.12681
M3 - SCORING: Journal article
C2 - 26811054
VL - 4
JO - Physiol Rep
JF - Physiol Rep
SN - 2051-817X
IS - 2
ER -