作　　者： ; ; ; ;

机构地区： 南方医科大学

出　　处： 《生物化学与生物物理进展》 2006年第3期241-246,共6页

摘　　要： 应用膜片钳全细胞记录模式研究了内源性一氧化氮(NO)对培养海马神经元延迟整流型钾电流的调控作用及其机制.给予NO合成酶的底物L-精氨酸(L-Arg,2mmol/L)可显著抑制海马神经元上的延迟整流型钾电流,但其同分异构体D-精氨酸(2mmol/L)对钾电流则无明显影响.并且,经一氧化氮合成酶抑制剂L-NAME(nomega-nitro-L-argininemethylester,0.5mmol/L)预处理后,L-Arg对钾电流的抑制作用消失,表明L-Arg抑制钾电流是通过产生NO而不是精氨酸本身.特异性鸟苷酸环化酶抑制剂ODQ(1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one,10!mol/L)预处理不影响L-Arg对钾电流的抑制作用,但巯基烷化剂NEM(N-ethylmaleimide,1mmol/L)预处理可完全阻断L-Arg的抑制效应.以上结果表明,内源性NO主要通过巯基亚硝化途径抑制海马神经元的延迟整流型钾电流. The modulating action and mechanism of endogenous nitric oxide （NO） on the delayed rectifier potassium currents in cultured hippocampal neurons were examined using whole-cell patch clamp techniques. L-arginine （L-Arg, 2 mmol/L）, a substrate of NO synthases, significantly suppressed the delayed rectifier K＋ currents in hippocampal neurons, while its isomer D-arginine （D-Arg, 2 mmol/L） exerted no effect. Moreover, pretreatment with NO synthase inhibitor L-NAME （0.5 mmol/L） completely blocked the suppressing effect by L-Arg, indicating that L-Arg exerted its modulation by producing NO but not by itself. No effect was found on the L-Arg-induced inhibition by 10 min pretreatment of 10 μmol/L ODQ （a specific inhibitor of gnanylate cyclase）. In contrast, thiol-alkylating agent N-ethylmaleimide （1 mmol/L） completely precluded L-Arg-induced inhibition on the whole K^＋ currents. The results indicate that endogenous NO modulates the delayed rectifier K^＋ currents in cultured hippocampal neurons mostly through S-nitrosylation.

关 键 词： 培养海马神经元 钾通道 巯基亚硝化 膜片钳

领　　域： [生物学]