脱氢表雄酮
神经活性类固醇
内分泌学
内科学
化学
兴奋剂
钠通道
蛋白激酶A
受体
钠
硫酸脱氢表雄酮
蛋白激酶C
膜片钳
激酶
γ-氨基丁酸受体
医学
生物化学
雄激素
激素
有机化学
作者
Zhengxiang Cheng,Dan-Mei Lan,Pei‐Ying Wu,Yanhua Zhu,Yi Dong,Lan Ma,Ping Zheng
标识
DOI:10.1016/j.expneurol.2007.10.004
摘要
Dehydroepiandrosterone sulphate is one of the most important neurosteroids. In the present paper, we studied the effect of dehydroepiandrosterone sulphate on persistent sodium currents and its mechanism and functional consequence with whole-cell patch clamp recording method combined with a pharmacological approach in the rat medial prefrontal cortex slices. The results showed that dehydroepiandrosterone sulphate inhibited the amplitude of persistent sodium currents and the inhibitory effect was significant at 0.1 μM, reached maximum at 1 μM and decreased with the increase in the concentrations of above 1 μM. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was canceled by the Gi protein inhibitor and the protein kinase C inhibitor, but not by the protein kinase A inhibitor. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was also canceled by the sigma-1 receptor blockers and the sigma-1 receptor agonist could mimic the effect of dehydroepiandrosterone sulphate. Dehydroepiandrosterone sulphate had no significant influence on neuronal excitability but could significantly inhibit chemical inhibition of mitochondria-evoked increase in persistent sodium currents. These results suggest that dehydroepiandrosterone sulphate inhibits persistent sodium currents via the activation of sigma-1 receptors–Gi protein–protein kinase C-coupled signaling pathway, and the main functional consequence of this effect of DHEAS is presumably to protect neurons under ischemia.
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