College of Life Science, Nankai University, 94 Weijin Rd, Nankai District, Tianjin 300071, PR China.
Toxicol Lett. 2010 Oct 5;198(2):171-6. doi: 10.1016/j.toxlet.2010.06.013. Epub 2010 Jun 25.
Since the melamine-contamination event happened in September 2008, there have been lots of studies about melamine toxicity, but very limited studies focused on central nervous system (CNS). In the present study, we investigated the effects of melamine (5x10(-4), 5x10(-5) and 5x10(-6)g/ml) on voltage-gated sodium channels (VGSCs) in hippocampal CA1 neurons using whole-cell patch-clamp recordings technique. The results showed that only 5x10(-4)g/ml melamine reduced the amplitude of voltage-gated sodium current (I(Na)). At the concentrations of 5x10(-5) and 5x10(-4)g/ml, melamine produced a hyperpolarizing shift in the steady-state activation curve of I(Na) and also enhanced the steady-state inactivate processing of I(Na). Action potential properties and the pattern of repetitive firing were examined using current-clamp recording, which indicated that peak amplitude and overshoot of the evoked single action potential were decreased. The half-width and the firing rate of repetitive firing were increased in a concentration-dependent manner. The data suggest that melamine alters the action potential of hippocampal CA1 neurons by impairing the functional properties of VGSCs, which may be the underlie mechanisms of neurotoxicity induced by melamine.
自 2008 年 9 月三聚氰胺污染事件发生以来，已有大量关于三聚氰胺毒性的研究，但仅有有限的研究集中在中枢神经系统（CNS）上。在本研究中，我们使用全细胞膜片钳记录技术研究了三聚氰胺（5x10(-4)、5x10(-5)和 5x10(-6)g/ml）对海马 CA1 神经元电压门控钠离子通道（VGSCs）的影响。结果表明，只有 5x10(-4)g/ml 的三聚氰胺降低了电压门控钠离子电流（I(Na)）的幅度。在 5x10(-5)和 5x10(-4)g/ml 的浓度下，三聚氰胺使 I(Na)的稳态激活曲线产生超极化偏移，并增强了 I(Na)的稳态失活过程。使用电流钳记录研究了动作电位特性和重复放电模式，结果表明，诱发的单个动作电位的峰值幅度和超射减小。重复放电的半宽度和放电率呈浓度依赖性增加。这些数据表明，三聚氰胺通过损害 VGSCs 的功能特性来改变海马 CA1 神经元的动作电位，这可能是三聚氰胺诱导神经毒性的潜在机制。
