孤啡肽对大鼠顶叶皮层神经元延迟整流钾电流的抑制作用

Inhibition of OFQ/N on the delayed rectifier potassium currents in acutely dissociated rat parietal cortical neurons

目的研究孤啡肽(orphanin FQ/nociceptin,OFQ/N)对大鼠顶叶皮层神经元延迟整流钾电流(IK)的影响,初步探讨其干扰学习记忆过程的离子机制。方法采用全细胞膜片钳技术,观察OFQ/N对急性分离的大鼠顶叶皮层神经元IK的作用。结果①OFQ/N明显抑制IK,并呈剂量依赖性(P<0.05)。②0.1μmol.L-1OFQ/N使IK的电流-电压(I-V)曲线降低(n=8,P<0.01)。③0.1μmol.L-1OFQ/N使IK激活曲线的半数激活电压(V1/2)和斜率因子(k)分别由给药前的(-43.4±6.1)mV和(11.5±1.1)mV变为给药后的(-19.1±4.6)mV和(17.3±3.2)mV(n=8,P<0.01)。④0.1μmol.L-1OFQ/N使IK失活曲线的半数失活电压(V1/2)和斜率因子(k)分别由给药前的(-68.8±2.6)mV和(16.5±1.7)mV变为给药后的(-76.8±2.8)mV(n=5,P<0.01)和(15.7±3.1)mV(n=5,P>0.05)。结论OFQ/N可抑制大鼠顶叶皮层神经元IK,使IK激活曲线右移,失活曲线左移。

Aim To study effects of orphanin FQ/nociceptin （OFQ/N） on the delayed rectifier potassium current （[K） in rat parietal cortical neurons and investigate the ionic basis for the behavioral observations of OFQ/N affecting learning and memory. Methods Effects of OFQ/N on IK were investigated by using the whole-cell patch clamp technique in acutely dissociated rat parietal cortical neurons. Results IK was inhibited by OFQ/N （0.01 -10 μmol·L^-1） in a concentration-dependent manner. At the concentration of 0. 1 μmol·L^-1 amplitudes of IK decreased at different membrane potentials by OFQ/N. OFQ/N （0.1 μmol·L^-1） shifted the activation curve of [K to positive potential from （-43.4±6.1） mV to （ -19.1 ±4.6） mV （n =8, P〈0.01） and changed its slope factor （k） from （11.5±1.1） mV to （17.3±3.2） mV （n =8,P〈0.01）. OFQ/N （0. 1 μmol·L^-1） caused a significant hyperpolarizing shift of the inactivation curvefrom （ -68.8 ±2.6） mV to （-76.8 ±2.8） mV（n =5,P〈0. 01 ）, but no significant effect on its K（ n = 5,P 〉 0. 05 ）. Conclusion OFQ/N inhibits IK of parietal cortical neurons of rats. It suggests that behavioral effects of OFQ/N on memory and learning may be partly mediated by the inhibitory effects of OFQ/N on IK.