EFFECTS OF TETRODOTOXIN, LIDOCAINE, VERAPAMIL, AND AHR-2666 ON OUABAIN-INDUCED DELAYED AFTER DEPOLARIZATIONS IN CANINE PURKINJE-FIBERS
EFFECTS OF TETRODOTOXIN, LIDOCAINE, VERAPAMIL, AND AHR-2666 ON OUABAIN-INDUCED DELAYED AFTER DEPOLARIZATIONS IN CANINE PURKINJE-FIBERS
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DOI：
10.1161/01.res.46.1.117
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发表时间：
1980-01-01
影响因子：
20.1
通讯作者：
DANILO, P
中科院分区：
文献类型：
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作者：
ROSEN, MR;DANILO, P
用标准微电极技术记录哇巴因（2 × 10 - 6）诱导的延迟后去极化（DAD）。10-7 M），并研究了DAD对快钠通道阻断剂河豚毒素（Tetrodotoxin）的反应（TTX，1 mg/l）;慢通道阻滞剂，维拉帕米（verap，1 mg/l）;假定的钙离子阻滞剂AHR-2666 [1-（N-甲基氨基甲酰基）-3-（间氯苯氧基）-吡咯烷]（AHR，45 mg/l）;利多卡因（利多卡因，4 mg/l），可增加稳态外向电流并降低背景内向电流。以1000-200 ms的周期长度驱动PF。哇巴因灌注30分钟诱导DAD，振幅为17.0 ± 1.5。1.5（平均值±）。TTX、Verap、AHR和Lido均使DAD幅值降低（P < 0.05）。为了相互比较药物的作用，构建了将DAD振幅与基本周期长度相关的图表，并使用嵌套方差分析测试了药物对所有周期长度下DAD振幅的相对影响幅度。Verap和AHR的作用相当，两者在短周期时（哇巴因对照组的37%）比长周期时（哇巴因对照组的76%）更能降低DAD振幅（P < 0.05）。利多有不同的效果，并减少DAD几乎相等的短（64%）和长（75%）周期长度。TTX的作用介于其他药物之间，与其他药物有显著性差异（P < 0.05）。AHR和verap似乎通过修改负责DAD的电流起类似作用，而lido似乎通过不同的机制起作用，可能是通过增加稳态外向电流。TTX的作用可能是通过影响Na+携带的瞬时内向电流或背景电流而实现的。
Standard microelectrode techniques were used to record delayed afterdepolarizations (DAD) induced by ouabain (2 .times. 10-7 M) in isolated canine Purkinje fibers (PF) and studied the response of DAD to the fast Na+ channel blocker, tetrodotoxin (TTX, 1 mg/l); the slow channel blocker, verapamil (verap, 1 mg/l); the putative Ca2+ blocker, AHR-2666 [1-(N-methylcarbamoyl)-3-(m-chlorphenoxy)-pyrrolidine] (AHR, 45 mg/l); and lidocaine (lido, 4 mg/l), which increases steady state outward current and decreases background inward current. PF were driven at cycle lengths of 1000-200 ms. Ouabain superfusion for 30 min induced DAD with amplitudes of 17.0 .+-. 1.5 (mean .+-. SE) mV at a cycle length of 200 ms. TTX, verap, AHR and lido all depressed DAD amplitude (P < 0.05). To intercompare the effects of the drugs, graphs were constructed relating DAD amplitude to basic cycle length, and the relative magnitude of effects of the drugs on DAD amplitude at all cycle lengths was tested using a nested analysis of variance. The effects of verap and AHR were equivalent, and both decreased DAD amplitude more at short (to 37% of ouabain control) than at long (to 76%) cycle lengths (P < 0.05). Lido had a different effect and decreased DAD nearly equivalently at short (to 64%) and long (to 75%) cycle lengths. The actions of TTX were intermediate between, and significantly different from, those of the other drugs (P < 0.05). AHR and verap appear to act similarly, by modifying the current responsible for DAD, whereas lido appears to act by a different mechanism, perhaps by increasing steady state outward current. The actions of TTX may be a result of its effect on the transient inward current or on a background current carried by Na+.