P107Electrical properties of human right atrial fibroblasts from patients in sinus rhythm and atrial fibrillation

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Abstract

Introduction

Cardiac fibroblasts can couple to cardiomyocytes via gap junctions and thus alter the electrical properties of the latter. The interaction between the 2 cell types might be of particular importance in the context of atrial fibrillation which is characterized by increased fibrosis. In order to understand the potential role of fibroblasts in atrial electric dysfunction, we compared the electrical properties of atrial fibroblasts isolated from patients in sinus rhythm (SR) and chronic atrial fibrillation (cAF).

Methods

Fibroblasts were isolated by outgrowth culture from right atrial biopsies and maintained in culture for up to 12 weeks. We used whole-cell patch clamp techniques to investigate ion currents and membrane potential.

Results

SR and cAF fibroblasts showed similar capacitance (SR: 43.6 ± 4.6 pF, n=33; cAF: 54.7 ± 5.1 pF, n = 17) and membrane potential (SR: -21.0 ± 4.3 mV, n = 14; cAF: -27.4 ± 4.8 mV, n = 16). In both groups, we observed fast activating outward currents with a mean threshold at -20 mV. Interestingly, current amplitude was significantly larger in SR than cAF cells at early stages of culture (SR: 23.8 ± 4.2 pA/pF, n = 15; cAF: 6.1 ± 1.0, n = 6; p < 0.05). After 3-5 weeks in culture, cells from both groups developed Na+ currents. The number of cells showing such currents was larger in cAF (SR: 15%; cAF: 38%), and increased with culture time. After 11-12 weeks of culture, Na+ currents were present in 87% of SR cells and 63% of cAF cells. Similarly, current amplitude was larger in cAF fibroblasts at early stages of culture (SR: 6.1 ± 2.0 pA/pF, n = 5; cAF: 17.4 ± 4.4 pA/pF, n = 6; p < 0.05) but comparable after 11-12 weeks of culture (SR: 25.0 ± 7.8 pA/pF, n = 13; cAF: 20.5 ± 4.2 pA/pF, n = 10, p = 0.6). Na+ currents were not altered by 100 nM Tetrodotoxin (TTX), but 10 μM TTX reduced current amplitude to 42% of control, suggesting that the channel involved is the cardiac TTX-resistant isoform Nav1.5. Some cells showing large Na+ currents at late stages of culture became excitable and could be stimulated to generate action potentials. AP parameters were similar in both SR and cAF.

Conclusions

The potential of atrial fibroblasts to become excitable is of significance for our understanding of their role in the pathophysiology of cAF. Since culture time diminishes the electrophysiological differences in properties of atrial fibroblasts derived from patients in SR and cAF, characterization of these cells as early as possible after isolation may provide an estimate close to their in vivo phenotype.

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