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Prevailing Effects of Ibutilide on Fast Delayed Rectifier K+ Channel.
The Journal of Membrane Biology ( IF 2.4 ) Pub Date : 2019-10-04 , DOI: 10.1007/s00232-019-00098-x Sodikdjon A Kodirov 1, 2, 3, 4 , Vladimir L Zhuravlev 1, 2 , Johannes Brachmann 1, 4
The Journal of Membrane Biology ( IF 2.4 ) Pub Date : 2019-10-04 , DOI: 10.1007/s00232-019-00098-x Sodikdjon A Kodirov 1, 2, 3, 4 , Vladimir L Zhuravlev 1, 2 , Johannes Brachmann 1, 4
Affiliation
Effects of ibutilide, a class III antiarrhythmic drug, on delayed rectifier potassium currents (IK) in freshly isolated guinea pig ventricular myocytes were studied. Experiments were performed using the whole-cell configuration of patch-clamp technique under blockade of L-type calcium currents (Cav1). Ibutilide at concentrations ranging between 10 nM and 100 µM inhibited IKr in dose-dependent manner with a half maximal effective concentration of 2.03 ± 0.74 µM (n = 5-10). The amplitude of tail currents activated by prepulse to + 20 mV was decreased from 253 ± 52 to 130 ± 25 pA (n = 8, p < 0.01) in the presence of 1 µM ibutilide. The envelope test revealed time-dependent changes in ratio of IK-tail/ΔIK during 0.2-2 s pulse durations in the absence of drug. With ibutilide, regardless of pulse duration, a relatively constant ratio was estimated, indicative of predominant involvement of IKr component. The slow IKs persisted to greater extent even at 100 μM ibutilide revealing a distinguishable selectivity toward the IKr component.
中文翻译:
伊布利特对快速延迟整流器K +通道的普遍影响。
研究了三类抗心律失常药物伊布利特对新鲜分离的豚鼠心室肌细胞中延迟整流钾电流(IK)的影响。在L型钙电流(Cav1)阻断下,使用膜片钳技术的全细胞配置进行了实验。浓度在10 nM和100 µM之间的依布利特以剂量依赖性方式抑制IKr,最大有效浓度的一半为2.03±0.74 µM(n = 5-10)。在存在1 µM依布利特的情况下,由预脉冲激活至+ 20 mV的尾电流幅度从253±52 pA降低至130±25 pA(n = 8,p <0.01)。包膜试验显示在不存在药物的情况下,在0.2-2 s的脉冲持续时间内IK-tail /ΔIK的比率随时间变化。使用依布利特,无论脉冲持续时间如何,都可以估算出相对恒定的比率,提示IKr成分占主要地位。即使在100μM依布利特的情况下,慢速IK仍能持续更大程度地显示出对IKr组分的明显选择性。
更新日期:2019-11-01
中文翻译:
伊布利特对快速延迟整流器K +通道的普遍影响。
研究了三类抗心律失常药物伊布利特对新鲜分离的豚鼠心室肌细胞中延迟整流钾电流(IK)的影响。在L型钙电流(Cav1)阻断下,使用膜片钳技术的全细胞配置进行了实验。浓度在10 nM和100 µM之间的依布利特以剂量依赖性方式抑制IKr,最大有效浓度的一半为2.03±0.74 µM(n = 5-10)。在存在1 µM依布利特的情况下,由预脉冲激活至+ 20 mV的尾电流幅度从253±52 pA降低至130±25 pA(n = 8,p <0.01)。包膜试验显示在不存在药物的情况下,在0.2-2 s的脉冲持续时间内IK-tail /ΔIK的比率随时间变化。使用依布利特,无论脉冲持续时间如何,都可以估算出相对恒定的比率,提示IKr成分占主要地位。即使在100μM依布利特的情况下,慢速IK仍能持续更大程度地显示出对IKr组分的明显选择性。