In humans, heart failure (HF), as a result of ventricular myocardial infarction (MI), predisposes the heart to atrial fibrillation (AF). This is caused by the associated structural and functional remodeling of the atria although the precise mechanisms are unknown. Previous studies indicate reduced L-type Ca2+ current (ICaL) in HF, in the presence of β-adrenergic (β-AR) stimulation (1). The aims of this study were to determine: 1) the effects of chronic MI in rabbits on AF threshold (AFT) in the presence of β-AR stimulation, and 2) the sensitivity of AFT to ICaL blockade to mimic the lowered ICaL seen in HF. Methods: MI was produced by ligation of the left descending coronary artery of adult male New Zealand White rabbits (~2.5kg). Animals were anaesthetised prior to thoracotomy (intravenous midazolam (0.2-0.5mg/kg, and ventilation with N2O/O2/1% halothane), and analgesia given post operatively (Vetergesic (0.04mg/kg)). Animals were sacrificed 8wks later with intravenous sodium pentobarbitone (100mg/kg). Sham operated animals were used as control (CON). Whole hearts were perfused in Langendorff mode with bicarbonate buffered Tyrode’s solution in the presence of isoproterenol (ISO 1 μM). AFT was measured as the median of 5 AF induction attempts using a train of constant current pulses (100Hz for 1s, 5-100mA in 5mA increments). Single myocytes from the left atria were enzymatically isolated and superfused with a HEPES buffered Krebs-Henseleit solution in the presence of the ISO. In a subset of experiments ICaL was blocked with nifedipine (NIF 2M). All experiments were carried out at 37˚C. Data are expressed as mean±SEM and compared using either unpaired t-test or repeated measures ANOVA, significant where P<0.05. Results: In isolated hearts, HF resulted in a ~60% reduction in mean median AFT; from 50.8 ±7.9mA to 19.6 ±4.4mA (n=17CON, 11HF. P<0.01), indicating an increased susceptibility to AF. In isolated cells, HF resulted in a ~35% reduction in average ICaL density compared to CON. A NIF dose-response curve for ICaL was constructed, in the presence of ISO, and 2 μM NIF found to reduce ICaL in CON myocytes by a similar degree (~40%) to that resulting from HF. In whole hearts (CON), 2 μM NIF reduced AFT by ~80%, from 49.4 ± 9.2mA to 10.0 ± 2.1mA (n=16. P<0.001). In the absence of β-AR stimulation, HF did not change AFT (n=7CON, 7HF. P>0.05) or ICaL density (n=13CON, 12HF. P>0.05). Conclusion: These data suggest that there is an association between the reduction of atrial ICaL by HF and the increased susceptibility to AF in HF, in the presence of β-AR stimulation. This study also highlights that, in HF-remodelled atria, Ca2+ channel blockade increases susceptibility to AF. This may have implications for the therapeutic use of Ca2+ channel blockers, since they are currently used for rate-control therapy in patients with AF.