Hyperpolarization activated cation current (I(f)) in cardiac myocytes from pulmonary vein sleeves in the canine with atrial fibrillation

OBJECTIVE: To investigate the characteristics of ectopic automaticity and cation current (I(f)) of cardiac myocytes from pulmonary vein sleeves (PVs) in canines with atrial fibrillation. METHODS: The canines (8–10 years old) were subjected to long-term, rapid atrial pacing (RAP) for 10 weeks, which induced the atrial fibrillation model. Disassociation of PVs of canines yielded single cardiac myocytes from a Landengorff column. Action potential, I(f) and hyperpolarisation activated cyclic nucleotide-gated (HCN) currents were measured with the patch-clamp technique. RESULTS: Compared with the control group, cardiac myocytes from the RAP canine PVs had spontaneous diastolic depolarization, shorter action potential duration, and larger I(f) densities. In the group of RAP cells, the half maximal activation potential (V(1/2)) was found to be less negative (−105.5 ± 5.2 mV) compared to control cells (−87.3 ± 4.9 mV). Current densities of I(f) were increased significantly by β-adrenergic receptor stimulation with isoproterenol and caused an acceleration of current activation. In contrast, I(f) currents in the RAP were reduced by carvedilol, a selective beta-adrenergic receptor. Another important finding is that HCN4-based channels may make a significant contribution to I(f) in PVs cells, but not HCN2. Meanwhile, HCN4 current significantly increases in canine PVs cardiac myocytes with RAP. CONCLUSIONS: The spontaneous action potential and larger I(f) current were observed in the PVs cardiac myocytes using RAP, which may contribute to more ectopic activity events to trigger and maintain atrial fibrillation.