PKC在孤啡肽抑制大鼠皮层神经元瞬时外向钾离子电流中的作用

Involvement of PKC in transient outward potassium current(I_A) inhibited by N/OFQ in acutely dissociated rat cerebral parietal cortical neurons

目的研究蛋白激酶C(PKC)对孤啡肽(N/OFQ)抑制大鼠皮层神经元瞬时外向钾电流(IA)的影响,初步探讨N/OFQ抑制IA的PKC信号途径。方法采用全细胞膜片钳技术,观察PKC特异性抑制剂chelerythrine对N/OFQ抑制大鼠皮层神经IA的影响。结果①与0.1μmol/L N/OFQ单独作用时,对IA的抑制作用相比,在cherythrine预处理的大鼠皮层神经元,在-40～-15 mV电压范围内,N/OFQ使IA的I-V曲线升高,而在-15～+60 mV电压范围内使IA的I-V曲线明显降低(n=10,P<0.05);②在指令电压+60 mV时,给予N/OFQ使IA的电流值由(1778.51±239.50)pA降至(1175.1±257.03)pA(n=10,P<0.05),抑制百分率为(33.93±6.62)%,与N/OFQ单独作用引起的(23.20±2.17)%的抑制率相比,具有显著性差异(n=10,P<0.05)。结论在不同电压下,chelerythrine对N/OFQ抑制大鼠皮层神经IA的影响不同,说明PKC在N/OFQ抑制IA中的作用因不同电压而具有双向性。

Objective To study the involvement of protein kinase C （PKC） in transient out- ward potassium current （Ⅰ_A ） inhibited by N/OFQ in acutely dissociated rat cerebral parietal cortical neurons. Methods Whole-cell voltage clamp technique was used to observe the effect of chelerythrine, a inhibitor of PKC, on the inhibition IA by Orphanin FQ/nociceptin （N/ OFQ） . Results ①Bath applications of N/OFQ resulted in bidirectional modulation of Ⅰ_A in different potentials in presence of chelerythrine （ n = 10, P 〈 0. 05 ）. ②The amplitude of Ⅰ_A was attenuated by N/OFQ at ＋ 60 mV in presence of chelerythrine （n = 10, P 〉 0. 05, com- pared with control）. N/OFQ＇ s percent inhibition on Ⅰ_A in presence of chelerythrine was （33.9 ± 6. 6 ）% that was more significantly than that in the control test without chelerythrine, （23.20 ± 2. 17）%. Conclusion N/OFQ likely modulates Ⅰ_A in a voltage-dependent mannerin presence of chelerythrine in acutely dissociated rat cerebral parietal cortical neurons.