Altered physiological functions and ion currents in atrial fibroblasts from patients with chronic atrial fibrillation

Autor: Edgar Büttner, Ursula Ravens, Claire Poulet, Dirk Westermann, Diana Lindner, Stephan R Künzel
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Cardiovascular Conditions
Disorders and Treatments
medicine.medical_specialty
Patch-Clamp Techniques
Physiology
Cellular differentiation
030204 cardiovascular system & hematology
Biology
Ion Channels
Signalling Pathways
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Fibrosis
Cell Movement
Physiology (medical)
Internal medicine
medicine
Humans
Channel blocker
Patch clamp
Heart Atria
Ion channel
Cells
Cultured
Aged
Cell Proliferation
Oligonucleotide Array Sequence Analysis
Original Research
Tetraethylammonium
Cell Differentiation
Fibroblasts
Middle Aged
medicine.disease
electrophysiology
Immunohistochemistry
Atrial fibrillation
Electrophysiology
030104 developmental biology
Endocrinology
chemistry
Chronic Disease
Tetrodotoxin
Female
Cellular Physiology
Transcriptome
Zdroj: Physiological Reports
ISSN: 2051-817X
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: