Lomonosov Moscow State University, Moscow, Russia.
Pirogov Russian National Research Medical University, Moscow, Russia.
Cardiovasc Drugs Ther. 2017 Dec;31(5-6):525-533. doi: 10.1007/s10557-017-6762-x.
A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium.
APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K currents in isolated myocytes.
In multicellular atrial preparations, 10 M niferidil effectively prolonged APs by 15.2 ± 2.8% at 90% repolarization level. However, even the highest tested concentrations, 10 M and 10 M failed to prolong APs more than 32.5% of control duration. The estimated concentration of niferedil for half-maximal AP prolongation was 1.13 × 10 M. Among the potassium currents responsible for AP repolarization phase, I was found to be almost insensitive to niferidil. However, another inward rectifier, I , was effectively suppressed by micromolar concentrations of niferidil with IC = 9.2 × 10 M. I was much less sensitive to the drug with IC = 2.26 × 10 M. The slow component of delayed rectifier, I , also demonstrated low sensitivity to niferidil-the highest used concentration, 10 M, decreased peak I density to 46.2 ± 5.5% of control. Unlike I , the rapid component of delayed rectifier, I , appeared to be extremely sensitive to niferidil. The IC was 1.26 × 10 M. I measured in ventricular myocytes was found to be less sensitive to niferidil with IC = 3.82 × 10 M.
Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I .
一种新型的 III 类抗心律失常药物尼非地平（RG-2）已被引入作为持续性心房颤动的有效治疗方法，但对其作用的离子机制知之甚少。本研究旨在研究尼非地平对豚鼠心房心肌动作电位（AP）波形和负责 AP 复极的钾电流的影响。
在多细胞心房标本中用尖锐玻璃微电极记录 AP。采用全细胞膜片钳技术测量分离心肌细胞中的 K 电流。
在多细胞心房标本中，10 μM 尼非地平可使 90%复极水平的 AP 有效延长 15.2±2.8%。然而，即使是测试的最高浓度，10 μM 和 10 μM 也未能使 AP 延长超过对照持续时间的 32.5%。尼非地平引起 AP 延长一半的估计浓度为 1.13×10-5 M。在负责 AP 复极相的钾电流中，I 几乎对尼非地平不敏感。然而，另一种内向整流电流 I 则被微摩尔浓度的尼非地平有效抑制，IC=9.2×10-5 M。I 对药物的敏感性较低，IC=2.26×10-5 M。延迟整流的慢成分 I 对尼非地平的敏感性也较低-最高使用浓度 10 μM 将峰值 I 密度降低至对照的 46.2±5.5%。与 I 不同，延迟整流的快速成分 I 似乎对尼非地平非常敏感。IC 为 1.26×10-5 M。在心室肌细胞中测量的 I 发现对尼非地平的敏感性较低，IC=3.82×10-5 M。
尼非地平通过抑制 I 延长豚鼠心房心肌的 AP。
