title: Nitric oxide modulation of voltage-gated calcium current by S-nitrosylation and cGMP pathway in cultured rat hippocampal neurons.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kuihuan
authors.initials: K
authors.lastname: Jian
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Xiong
authors.initials: X
authors.lastname: Cao
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Zhu
authors.forename: Man-Lung
authors.initials: ML
authors.lastname: Fung
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D046509:Tissue Culture Techniques
chemical_list: D015220:Calcium Channels; D011073:Polyamines; C005391:diethylenetriamine; D009569:Nitric Oxide; D006152:Cyclic GMP; D009584:Nitrogen