Jian Kuihuan, Chen Ming, Cao Xiong, Zhu Xin-Hong, Fung Man-Lung, Gao Tian-Ming
Department of Anatomy and Neurobiology, Southern Medical University, Guangzhou 510515, China.
Biochem Biophys Res Commun. 2007 Aug 3;359(3):481-5. doi: 10.1016/j.bbrc.2007.05.113. Epub 2007 May 25.
Nitric oxide (NO) plays an important role in many physiological and pathophysiological processes in the brain. In this study, we examined the mechanistic effects of an NO donor, diethylenetriamine/nitric oxide adduct (DETA/NO) on the voltage-gated calcium currents in cultured rat hippocampal neurons. DETA/NO stimulated the calcium currents and slightly increased the channel sensitivity to depolarizing voltages. The effect of DETA/NO on the calcium current was blocked by either depleting the NO in DETA/NO or by pretreating the neurons with NEM, a thiol-specific alkylating agent, suggesting an involvement of S-nitrosylation in the current response to NO. In addition, activation of the cGMP pathway by 8-Br-cGMP inhibited the calcium current in the neurons. Also, inhibition of guanylyl cyclase by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) increased the current response to DETA/NO. Taken together, our results demonstrate that both S-nitrosylation and cGMP pathway are involved in the NO modulation of the hippocampal calcium current.
一氧化氮（NO）在大脑的许多生理和病理生理过程中发挥着重要作用。在本研究中，我们检测了一种NO供体，二乙烯三胺/一氧化氮加合物（DETA/NO）对培养的大鼠海马神经元电压门控钙电流的作用机制。DETA/NO刺激了钙电流，并略微增加了通道对去极化电压的敏感性。通过耗尽DETA/NO中的NO或用硫醇特异性烷基化剂NEM预处理神经元，可阻断DETA/NO对钙电流的影响，这表明S-亚硝基化参与了对NO的电流反应。此外，8-溴-cGMP激活cGMP途径可抑制神经元中的钙电流。同样，1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ）抑制鸟苷酸环化酶可增加对DETA/NO的电流反应。综上所述，我们的结果表明，S-亚硝基化和cGMP途径均参与了NO对海马钙电流的调节。
