Kotake H, Hisatome I, Matsuoka S, Miyakoda H, Hasegawa J, Mashiba H
1st Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Cardiovasc Res. 1990 Jan;24(1):42-6. doi: 10.1093/cvr/24.1.42.
STUDY OBJECTIVE - To examine the effect of 9-amino-1,2,3,4-tetrahydroacridine (THA), a compound similar to the K+ blocker 4-aminopyridine, on potassium channels in the sinoatrial node. DESIGN - The pacemaking portion of rabbit sinoatrial nodes was studied using the double microelectrode voltage clamp method in the presence of THA at various concentrations. MEASUREMENTS AND RESULTS - Above 1 mumol.litre-1, THA prolonged the spontaneous cycle length and the transmembrane action potential duration at 50% repolarisation. Above 10 mumol.litre-1, the compound also decreased the maximum rate of rise, the action potential amplitude, and the rate of diastolic depolarisation. Under voltage clamp conditions, THA reduced the time dependent K+ current (IK) in a dose dependent manner. Neither the decay process of IK nor its activation process were altered by THA. CONCLUSIONS - THA depresses sinoatrial node IK without changing its kinetics. Thus it may inhibit the open state of the potassium channels.
研究目的——研究与钾离子阻滞剂4-氨基吡啶类似的化合物9-氨基-1,2,3,4-四氢吖啶（THA）对窦房结钾通道的作用。设计——在不同浓度的THA存在下，采用双微电极电压钳法研究兔窦房结的起搏部分。测量与结果——浓度高于1 μmol·L⁻¹时，THA延长了自发周期长度和复极化50%时的跨膜动作电位持续时间。浓度高于10 μmol·L⁻¹时，该化合物还降低了最大上升速率、动作电位幅度和舒张期去极化速率。在电压钳条件下，THA以剂量依赖性方式降低时间依赖性钾电流（IK）。THA既未改变IK的衰减过程，也未改变其激活过程。结论——THA抑制窦房结IK而不改变其动力学。因此，它可能抑制钾通道的开放状态。
