Abstract 10635: Changes in Cardiac Fibroblast Ion Channel Expression and Atrial Remodelling
Background: Cardiac fibroblasts are pivotal in remodeling and arrhythmogenesis, by secreting excess ECM proteins (fibrosis) and coupling to/altering cardiomyocyte electrophysiology. This study characterized atrial fibroblast ionic remodeling in 2 canine AF models: atrial tachycardia remodeling (ATR) and CHF, with fibrosis potentially occurring in both but particularly CHF.
Methods: Freshly isolated LA fibroblasts were obtained from control (CTL), ATR (1 wk atrial tachypacing 400 bpm) and CHF (2 wk ventricular tachypacing 240 bpm) dogs. Whole cell patch clamp was used to record K+ currents.
Results: Fibroblasts had membrane capacitances of 16.7±0.1 (n=75), 18.4±1.4 (n=25), 28.5±1.9 (n=41, P<0.001 vs CTL) pF in CTL, ATR and CHF, respectively. Resting potential averaged -31±2 mV in CTL (n=16), -33±3 mV in ATR (n=10), and -41±1.9 mV in CHF (n=33, P<0.05 vs CTL) fibroblasts. Clear Ba2+ sensitive (300 μ M) inwardly rectifying K+ (Kir) current was recorded (Figure A). At -120 mV, Kir current averaged -2.4±1.6 in CTL (n=11) and -3.8±0.6 (n=4) pA/pF in CHF fibroblasts (Figure B). Time- and voltage-dependent K+ (Kv) currents were elicited by 500-ms voltage steps (Figure C). Different time-dependencies were observed in individual cells, with the most common pattern, rapid activation and slow inactivation, seen in 56%. Kv-currents were reversibly suppressed by TEA (mean IC50 0.7 mM). At +70 mV, 30-mM TEA-sensitive current averaged 11.3±1.6 pA/pF in CTL (n=20), 6.5±1.5pA/pF in ATR (n=16, P<0.01 vs CTL) and 3.1±0.4 pA/pF in CHF (n=20, P<0.001 vs CTL) fibroblasts (Figure D). ATR and CHF did not alter TEA sensitivity.
Conclusions: Atrial fibroblasts express a variety of K+ current types. AF pathologies associated with fibrotic remodeling alter these currents, upregulating Kir currents and resting potential, downregulating Kv outward currents. These changes in fibroblast electrophysiology may play important roles in fibrosis development and arrhythmogenesis leading to AF.
- © 2011 by American Heart Association, Inc.