Department of Pharmacology and Therapeutic, Universidad Autónoma de Madrid, IRYCIS, Av. Arzobispo Morcillo 4, 28029, Madrid, Spain.
Instituto Teófilo Hernando, Facultad de Medicina, Departamento de Farmacología, Universidad Autónoma de Madrid, IRYCIS, Av. Arzobispo Morcillo 4, 28029, Madrid, Spain.
Pflugers Arch. 2018 Aug;470(8):1221-1230. doi: 10.1007/s00424-018-2144-x. Epub 2018 Apr 21.
In a previous study, we pointed out that the neurotoxic action evoked by methylmercury (MeHg), a potent environmental pollutant responsible for fatal food poisoning, is associated with alterations of cellular excitability by irreversible blockade of sodium and calcium currents. Here, we investigated the MeHg effects on synaptic transmission and neuronal plasticity using extracellular field recording in CA1 area of rat hippocampal slices. MeHg caused a fast and drastic depression of evoked field excitatory postsynaptic potentials (fEPSPs) in a concentration-dependent manner with an IC of 25.7 μM. This depression was partially caused by the irreversible reduction of axon recruitment deduced from the decrement of the fiber volley (FV) amplitude. Nevertheless, this MeHg-induced synaptic depression represents a true reduction of synaptic efficacy, as judged by input/output curves. In addition, a reduction on presynaptic release of glutamate was detected with the paradigm of paired-pulse facilitation during MeHg application. Moreover, MeHg also reduced population spike (PS) ampxlitude, and this effect was more prominent when the PS was evoked by ortodromic stimulation than by antidromic stimulation. Interestingly, despite these strong effects of MeHg on synaptic transmission and excitability, this compound did not modify the induction of long-term synaptic potentiation (LTP). The effects described here for MeHg were irreversible or very slowly reversible after drug wash-out. In summary, the blockade of sodium and calcium channels by MeHg affects synaptic transmission and cellular excitability but not synaptic plasticity.
在之前的研究中，我们指出，甲基汞（MeHg）的神经毒性作用与钠离子和钙离子电流的不可逆阻断导致的细胞兴奋性改变有关，而甲基汞是一种强效的环境污染物，可导致致命的食物中毒。在这里，我们使用大鼠海马切片 CA1 区的细胞外场记录来研究 MeHg 对突触传递和神经元可塑性的影响。MeHg 以浓度依赖的方式快速且剧烈地抑制了诱发的场兴奋性突触后电位（fEPSP），IC 为 25.7μM。这种抑制部分是由于轴突募集的不可逆减少，这是从纤维传播（FV）幅度的减少推断出来的。然而，这种 MeHg 诱导的突触抑制代表了突触效能的真正降低，这可以通过输入/输出曲线来判断。此外，在应用 MeHg 期间，通过成对脉冲易化范式检测到谷氨酸前释放的减少。此外，MeHg 还降低了群体锋电位（PS）幅度，并且当 PS 通过顺行刺激而不是逆行刺激诱发时，这种效应更为明显。有趣的是，尽管 MeHg 对突触传递和兴奋性有很强的影响，但这种化合物并没有改变长时程突触增强（LTP）的诱导。MeHg 的这些作用是不可逆的，或者在药物洗脱后非常缓慢地可逆。总之，MeHg 对钠离子和钙离子通道的阻断会影响突触传递和细胞兴奋性，但不会影响突触可塑性。
