The class III antiarrhythmic agent E-4031 selectively blocks the inactivating inward-rectifying potassium current in rat anterior pituitary tumor cells (GH3/B6 cells)
The class III antiarrhythmic agent E-4031 selectively blocks the inactivating inward-rectifying potassium current in rat anterior pituitary tumor cells (GH3/B6 cells)
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III类抗心律失常药E-4031选择性阻断大鼠垂体前叶肿瘤细胞（GH3/B6细胞）失活的内向整流钾电流
DOI：
10.1007/s004240050356
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
J. Schwarz
中科院分区：
文献类型：
--
作者：
F. Weinsberg;C. Bauer;J. Schwarz
用高钾溶液浸泡GH 3/B6细胞，记录细胞超极化诱发的钾电流，以观察Ⅲ类抗心律失常药E-4031对失活的内向整流钾电流（IK，IR）的影响。E-4031有效地阻断IK，IR，IC 50值为10 nM。浓度≥ 1 μM时实现的IK、IR完全阻断显示存在非灭活外向整流电流，该电流有助于在对照条件下记录的膜电流。IK、IR阻断的时间依赖性取决于E-4031的浓度。WAY-123，398（10 μM）也能完全阻断IK、IR，而索他洛尔（100 μM）几乎无效。镧（100 μM）对IK、IR的影响很小，E-4031对钠、钙和电压依赖性外向整流钾电流无影响，提示镧对GH 3/B6细胞IK、IR有选择性阻断作用。在含有16 mM钾的外部溶液中，E-4031敏感电流在钾平衡电位EK为正的宽电位范围内作为稳定的外向电流存在。在许多（但不是全部）细胞中，E-4031诱导动作电位频率增加，表明IK、IR在控制细胞兴奋性方面发挥重要作用。我们的实验表明，E-4031是一个有价值的工具，在表征IK，IR及其生理功能。
Abstract Hyperpolarization-elicited potassium currents in GH3/B6 cells bathed in high-potassium external solution were recorded to assess effects of the class III antiarrhythmic agent E-4031 on the inactivating inward-rectifying potassium current (IK,IR). E-4031 potently blocked IK,IR with an IC50 value of 10 nM. The complete block of IK,IR achieved with concentrations ≥ 1 μM revealed the presence of a non-inactivating outward-rectifying current which contributed to the membrane currents recorded under control conditions. The time dependence of the IK,IR block depended on the concentration of E-4031. Two other methanesulfonanilides were investigated: WAY-123,398 (10 μM) also totally blocked IK,IR, while sotalol (100 μM) was almost ineffective. Also lanthanum (100 μM) had only a very small effect on IK,IR. E-4031 did not affect sodium, calcium and voltage-dependent outward-rectifying potassium currents, suggesting a selective block of IK,IR in GH3/B6 cells. In an external solution containing 16 mM potassium, the E-4031-sensitive current was present as a steady outward current within a broad potential range positive to the potassium equilibrium potential, EK. In many, but not all, cells E-4031 induced an increase in the frequency of action potentials suggesting an important role of IK,IR in controlling cell excitability. Our experiments show that E-4031 is a valuable tool in characterizing IK,IR and its physiological function.
GH3垂体细胞失活K电流及其化学试剂修饰。
DOI：
10.1113/jphysiol.1989.sp017550
发表时间：
1989
期刊：
The Journal of physiology
影响因子：
--
作者：
Oxford,GS;Wagoner,PK
通讯作者：
Wagoner,PK
克隆的人类内向整流 K 通道作为 III 类甲磺酰苯胺的靶标。
影响因子：
20.1
作者：
Kiehn,J;Wible,B;Ficker,E;Taglialatela,M;Brown,AM
通讯作者：
Brown,AM