title: Apamin modulates electrophysiological characteristics of the pulmonary vein and the Sinoatrial Node.
abstract: 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.
  
  
  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, 10 nM). 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 ± 0.1 Hz, 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan.
authors.forename: Wei-Ta
authors.initials: WT
authors.lastname: Chen
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chen
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lu
authors.forename: Yu-Hsun
authors.initials: YH
authors.lastname: Kao
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Huang
authors.forename: Yung-Kuo
authors.initials: YK
authors.lastname: Lin
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D032342:Muscle Cells / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors*
chemical_list: D002121:Calcium Channel Blockers; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin
keywords: Apamin; Small-conductance calcium-activated potassium current; atrial fibrillation; pulmonary vein; sinoatrial node