Institute for Electronics and Informatics, South-Central University for Nationalities, Wuhan 430074, PR China.
Brain Res. 2010 Mar 8;1318:23-32. doi: 10.1016/j.brainres.2009.12.047. Epub 2010 Jan 4.
Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] is a dimeric AChE inhibitor derived from tacrine with a potential to treat Alzheimer's disease. Actions of bis(7)-tacrine on ligand-gated ion channels and voltage-gated cation channels have been identified on neurons of both central and peripheral nervous systems. In the present study, the effect of bis(7)-tacrine was investigated on the K(V)4.2 encoded potassium currents expressed in Xenopus oocytes and the transient A-type potassium current (I(K(A))) on rat DRG neurons. Bis(7)-tacrine suppressed recombinant Kv4.2 potassium channels in a concentration-dependent manner, with IC(50) value of 0.53+/-0.13 muM. Tacrine also inhibited Kv4.2 channels, but with a much lower potency (IC(50) 74+/-15 muM).The possible mechanisms underlying the inhibition on potassium currents by bis(7)-tacrine/tacrine could be that inactivation of the transient potassium currents was accelerated and recovery of the native or Kv4.2 expressed potassium currents was suppressed by bis(7)-tacrine/tacrine.
双（7）-他克林[双（7）-四氢氨基吖啶]是一种源自他克林的二聚乙酰胆碱酯酶抑制剂，具有治疗阿尔茨海默病的潜力。双（7）-他克林在中枢和周围神经系统的神经元上的配体门控离子通道和电压门控阳离子通道的作用已被确定。在本研究中，研究了双（7）-他克林对在非洲爪蟾卵母细胞中表达的 K(V)4.2 编码钾电流和大鼠 DRG 神经元上的瞬时 A 型钾电流（I(K(A)))的影响。双（7）-他克林以浓度依赖性方式抑制重组 Kv4.2 钾通道，IC（50）值为 0.53+/-0.13 muM。他克林也抑制 Kv4.2 通道，但效力低得多（IC（50）为 74+/-15 muM）。双（7）-他克林/他克林对钾电流的抑制作用的可能机制是，双（7）-他克林/他克林加速了瞬时钾电流的失活，并抑制了天然或 Kv4.2 表达的钾电流的恢复。
