Abstract 20971: Differential Electrophysiological Properties of Atrial Fibroblasts From AF versus Sinus Rhythm Patients
Background: Cardiac fibrosis is associated with a variety of heart diseases including atrial fibrillation (AF). Cardiac fibroblast is the major cell type in cardiac fibrogenesis cascade. However, the biological as well as electrophysiological properties of cardiac fibroblasts are not fully understood. In this study, we investigated the functional expression of voltage-gated and non-voltage-gated ion channels in artial fibroblasts from AF patients and SR patients, and their contribution to atrial fibrogenesis.
Methods: With informed consent, right atrial biopsies were obtained from AF patients or sinus rhythm (SR) patients undergoing cardiac surgery. Fibroblasts were dissociated from the biopsy samples from SR patients or AF patients. The freshly isolated cells were used for patch-clamp and ratio Ca2+-imaging experiments.
Results: We found that there are two types of voltage-gated outward potassium channels in the fibroblasts from SR patients: one is transient outward potassium current (Ito), and the other one is sustained delayed rectifier potassium channel (Isus). Both Ito and Isus can be blocked by 4-AP and TEA. Interestingly, Ito was not observed in fibroblasts isolated from AF patients, albeit both Ito and Isus were readily recorded in fibroblasts from SR patients, suggesting that Ito was down-regulated in AF fibroblasts. The non-voltage gated non-selective channel TRPM7 current in AF fibroblasts is ∼ 3 fold larger than that in SR fibroblasts. The up-regulated TRPM7 and TRPM7-mediated Ca2+.signals regulate AF fibroblast differentiation. Other voltage gated channels, including voltage gated Ca2+ or Na+ currents were not recorded in either AF fibroblasts or SR fibroblasts.
Conclusions: The transient outward potassium current (Ito) is down-regulated whereas TRPM7 is up-regulated in AF fibroblasts. The up-regulated TRPM7 is involved in the increased proliferation, differentiation and collagen synthesis in AF fibroblasts. Future study will be focused on understanding how Ito is down-regulated in AF fibroblasts, the molecular mechanisms regulating the potassium channels in human atrial fibroblasts, and the contribution of potassium channels in fibroblast biology and fibrogenesis cascade.
- © 2010 by American Heart Association, Inc.