期刊
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
卷 43, 期 9, 页码 957-963出版社
WILEY-BLACKWELL
DOI: 10.1111/eci.12125
关键词
Apamin; atrial fibrillation; pulmonary vein; sinoatrial node; Small-conductance calcium-activated potassium current
资金
- National Science Council of Taiwan [NSC99-2314-B-016-034-MY3, NSC99-2628-B-038-011-MY3, NSC100-2628-B-038-001-MY4, NSC100-2314-B-038-027-MY3]
- Taipei Medical University-Wan Fang Hospital [102swf01]
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.
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