一氧化氮对大鼠黑质致密部神经元自发放电及Glu能和GABA能传入活动的影响

Modulation of neuronal spontaneous discharge and Glu-ergic,GABAergic inputs activity by nitric oxide in substantia nigra pars compacta of rats

目的:研究一氧化氮(NO)对大鼠黑质致密部(SNc)神经元自发放电活动及对谷氨酸(Glu)、γ-氨基丁酸(GABA)能神经纤维输入活动的影响,为进一步研究Parkinson病(PD)的发病机制奠定神经生理学基础。方法:采用微电泳技术观察NO供体硝普钠(SNP),Glu及GABA对SNc神经元自发放电活动的影响及神经递质间的相互作用。结果:微电泳SNP使81.25%(39/48)受试神经元自发放电频率加快,此兴奋性作用与微电泳电流强度正相关,随着电流强度的增加(20nA～80nA),SNc神经元自发放电频率进一步加快。在35个受试神经元上分别微电泳Glu或GABA后,可以观察到分别有31神经元兴奋或所有神经元表现为抑制作用。在已经被Glu兴奋的31个神经元上同时微电泳SNP可使SNc神经元自发放电频率进一步加快。相反,在微电泳GABA的同时应用SNP可使已经被抑制的神经元放电频率增加。结论:NO对SNc神经元产生兴奋性作用。NO与Glu、GABA能投射在SNc有汇聚作用,NO协同Glu对SNc神经元产生兴奋性作用,但拮抗GABA对SNc神经元抑制性作用。

Objective： To investigate the effects of the nitric oxide on the spontaneous discharge and Glu-ergic, GABAergic inputs activity of the substantia nigra pars compacta （SNc） neurons in rats, so as to provide neuroelectrophysiologic basic for studing pathogenesis of Parkinson＇s disease （PD）. Methods： Microiontophoresis technique was used to examine the effects of sodium nitroprusside （SNP） , the nitric oxide （NO） donator, Glu and GABA on the spontaneous discharge of the SNc neurons and the interaction between neurotransmitters. Results： Administration of SNP produced increase in firing rates on 81.25 percent （39/48） of tested SNc neurons. The SNP-induced excitation was current-dependent. As the microiontophoretic current increased （20nA -80nA） , there was further increase in SNc neuronal firing rates. The effects of Glu or GABA on 35 SNc neurons were observed respectively. The firing rates of 31 SNc neurons（31/35） were increased by Glu ; all of SNc neurons were inhibited by GABA. In the presence of Glu, administration of SNP resulted in a further increase in the firing rates in 31 tested neurons （excited already by Glu）. However, in the presence of GABA, administration of SNP could resist GABA-induced inhibitory （ compared to GABA application alone）. Conclusion： These results demonstrate clearly that NO have a tense excitation on the SNc neurons. The NOergie, Glu-ergic and GABAergic inputs activities converge on the same SNc neurons; NO coordinated Glu-induced excitation and antagonized GABA-induced inhibition.