Nitric oxide modulation of voltage-gated calcium current by S-nitrosylation and cGMP pathway in cultured rat hippocampal neurons.
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.
Jian
Kuihuan
K
Department of Anatomy and Neurobiology, Southern Medical University, Guangzhou 510515, China.
Chen
Ming
M
Cao
Xiong
X
Zhu
Xin-Hong
XH
Fung
Man-Lung
ML
Gao
Tian-Ming
TM
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
D015220:Calcium Channels; D011073:Polyamines; C005391:diethylenetriamine; D009569:Nitric Oxide; D006152:Cyclic GMP; D009584:Nitrogen