Apamin modulates electrophysiological characteristics of the pulmonary vein and the Sinoatrial Node
Apamin modulates electrophysiological characteristics of the pulmonary vein and the Sinoatrial Node
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DOI：
10.1111/eci.12125
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发表时间：
2013-09-01
影响因子：
5.5
通讯作者：
Chen, Yi-Jen
中科院分区：
文献类型：
--
作者：
Chen, Wei-Ta;Chen, Yao-Chang;Chen, Yi-Jen
背景小电导钙活化钾（SK）通道在心房电生理中起重要作用。阻断SK通道延长动作电位（AP）持续时间并减弱电重构。SK阻断对肺静脉（PV）和窦房结（SAN）的影响尚不清楚。材料与方法采用常规微电极记录apamin （1,10 nm）治疗前后SANs和未剥落兔离体pv的AP。利用全细胞膜片钳技术，研究了分离的单个PV和SAN肌细胞的SK电流。结果在未剥落的PV （n = 6）中，apamin（1和10 nM）增加PV自发活性（从1.8 +/- 0.2 Hz增加到2.4 +/- 0.2 Hz和2.3 +/- 0.2 Hz, P < 0.05），增加PV张力42 +/- 14%和37 +/- 11%。相反，在剥落的PV （n = 6）中，apamin（1和10 nM）降低了自发活性（从2.2 +/- 0.3 Hz降至1.9 +/- 0.2 Hz和1.8 +/- 0.2 Hz, P < 0.05），延长了AP持续时间，但没有改变PV张力。此外，apamin（1和10 nM）降低了SAN的自发活性（从2.8 +/- 0.1Hz降至2.4 +/- 0.1Hz和2.4 +/- 0.1Hz, P < 0.05）并延长了AP持续时间（n = 6）。SAN心肌细胞的SK电流大于PV心肌细胞。与PV心肌细胞（n = 16）相比，apamin （10 nM）治疗导致分离的单个SAN （n = 17）的自发活性下降更大（25 +/- 8% vs. 20 +/- 13%, P < 0.05）。结论小电导钙活化钾通道在SAN和PV自发活性及AP形态中起关键作用。无论是否依赖内皮细胞，维生素a都可能调节PV电活动。
Background Small-conductance calcium-activated potassium (SK) channels play an important role in atrial electrophysiology. Blocking SK channels prolongs action potential (AP) duration and attenuate electrical remodelling. The effects of SK blocking on the pulmonary vein (PV) and the sinoatrial node (SAN) remain unclear.Materials and methods Conventional microelectrodes were used to record the AP in SANs and in isolated rabbit PVs with and without denudation before and after treatment with apamin (1, 10nM). Using the whole-cell patch-clamp technique, the SK current was investigated in isolated single PV and SAN myocytes.Results In nondenudated PVs (n = 6), apamin (1 and 10 nM) increased PV spontaneous activity (from 1.8 +/- 0.2 Hz to 2.4 +/- 0.2 Hz and 2.3 +/- 0.2 Hz, P < 0.05) and increased the PV tension by 42 +/- 14% and 37 +/- 11%. Conversely, in denudated PVs (n = 6), apamin (1 and 10 nM) decreased spontaneous activity (from 2.2 +/- 0.3 Hz to 1.9 +/- 0.2 Hz and 1.8 +/- 0.2 Hz, P < 0.05) and prolonged AP duration without changing PV tensions. Additionally, apamin (1 and 10 nM) decreased spontaneous activity (from 2.8 +/- 0.1 Hz to 2.4 +/- 0.1Hz, and 2.4 +/- 0.1 Hz, P < 0.05) and prolonged AP duration in SAN (n = 6). SAN myocytes had larger SK currents than did PV cardiomyocytes. Treatment with apamin (10 nM) resulted in a greater decrease (25 +/- 8 vs. 20 +/- 13%, P < 0.05) in spontaneous activity in isolated single SAN (n = 17) vs. PV cardiomyocytes (n = 16).Conclusion Small-conductance calcium-activated potassium channels play a key role in SAN and PV spontaneous activity and AP morphology. Apamin may modulate PV electrical activity with and without endothelium dependence.