他克林对培养大鼠海马神经元延迟整流钾电流和瞬间外向钾电流的影响

Inhibition of tacrine on delayed rectifier and transient outward potassium currents in cultured rat hippocampal neurons

目的 研究他克林对培养大鼠海马神经元上延迟整流钾电流 (IK)和瞬间外向钾电流 (IA)的影响。方法大鼠海马神经元原代培养 ,全细胞膜片钳记录培养大鼠海马神经元上电压依赖性外向钾电流和瞬间外向钾电流变化。结果 他克林明显抑制海马神经元延迟整流钾电流和瞬间外向钾电流 ,呈浓度依赖性 ,对延迟整流钾电流的敏感性高于瞬间外向钾电流。 3 0 μmol·L- 1他克林显著影响IK 和IA 稳态激活曲线 ,使所有电流的V1 2 左移。结论 他克林明显抑制延迟整流钾电流和瞬间外向钾电流 。

Aim To study the effects of tacrine on I K and I A potassium current in primary cultured rat hippocampal neurons. Methods Whole cell patch clamp and primary rat hippocampal neuron cultures were used. Results Tacrine was shown to reduce the amplitude of I K and I A, in concentra tion-dependent manners. The IC 50 s at +40 mV for reduction of I K and I A were 23 and 52 6 μmol·L -1 , respectively. Tacrine (30 μmol·L -1 ) shifted the steady state activation of I K and I A to negative potentials by 12 and 15 mV, respectively. The V 1/2 of activation curves for I K current before and after the application of tacri ne were (6 7±1 4) mV and ( -5 4 ±1 3) mV, respectively. The k of act ivation curves for I K current was 13 4+1 3 and 12 5+1 4 without and wi th tacrine, respectively. The V 1/2 of activation curve for I A cu rrent were ( -9 9 ±2 6) mV and ( -24 ±5) mV in the absence and presence of tacrine, respectively, and the k value was not changed. Conclusion Tacrine inhibited I K and I A currents in rat hippocampal neurons and it is more potent for blocking I K.