Bis(3)-tacrine inhibits the sustained potassium current in cultured rat hippocampal neurons.
Bis(3)-tacrine inhibits the sustained potassium current in cultured rat hippocampal neurons.
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DOI：
10.33549/physiolres.933354
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发表时间：
2017-02
影响因子：
2.1
通讯作者：
Ruojian Wen;D. Huang;Y. Zhang;Y-W Liu
中科院分区：
文献类型：
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作者：
Ruojian Wen;D. Huang;Y. Zhang;Y-W Liu
双（3）-他克林是一种二聚体乙酰胆碱酯酶抑制剂，来源于他克林，具有治疗阿尔茨海默病的潜力。最近有报道，它作为一种快速的解离速率拮抗剂的NMDA受体与中等亲和力。本研究采用全细胞膜片钳技术探讨双（3）-他克林对培养大鼠海马神经元自发性持续钾电流的影响。我们发现，双（3）-他克林以可逆和浓度依赖的方式抑制持续钾电流的幅度，其效力比他克林高两个数量级。在0-+60 mV之间，抑制作用不依赖于电压。双（3）-他克林和他克林抑制持续钾电流的IC（50）值分别为0.45+/-0.07和50.5+/-4.8 microM。I-V曲线显示，与相同浓度的他克林相比，双（3）-他克林（1 μ M）对持续钾电流的抑制作用更强。双（3）-他克林使电流的激活曲线超极化11.2 mV，但电流的稳态失活不受影响。
Bis(3)-tacrine is a dimeric AChE inhibitor derived from tacrine with a potential to treat Alzheimer's disease. It was recently been reported to act as a fast off-rate antagonist of NMDA receptors with moderate affinity. In the present study, we aimed to explore whether bis(3)-tacrine could modulate the function of native sustained potassium current in cultured rat hippocampal neurons using whole-cell patch-clamp technique. We found that bis(3)-tacrine inhibited the amplitude of sustained potassium current in a reversible and concentration-dependent manner, with a potency two orders of magnitude higher than that of tacrine. The inhibition was voltage-independent between 0 to +60 mV. The IC(50) values for bis(3)-tacrine and tacrine inhibition of sustained potassium current were 0.45+/-0.07 and 50.5+/-4.8 microM, respectively. I-V curves showed a more potent inhibition of sustained potassium current by bis(3)-tacrine (1 microM) compared to tacrine at the same concentration. Bis(3)-tacrine hyperpolarized the activation curve of the current by 11.2 mV, albeit leaving the steady-state inactivation of the current unaffected.