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

心房颤动犬肺静脉袖状心肌细胞超极化激活阳离子电流(I(f))

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作者:Jia-Yue Li, Hong-Juan Wang, Bin Xu, Xue-Ping Wang, Yi-Cheng Fu, Mei-Yan Chen, De-Xian Zhang, Yan Liu, Qiao Xue, Yang Li

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.

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.

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.

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.

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