Krüger K, Höing T, Bensch W, Diepgrond V, Ahnefeld M, Madeja M, Binding N, Musshoff U
Institute of Physiology I, University of Münster, Robert-Koch-Str. 27a, D-48149 Münster, Germany.
Neurotoxicology. 2007 Jan;28(1):114-25. doi: 10.1016/j.neuro.2006.08.004. Epub 2006 Aug 22.
The aim of this study was to investigate the effects of monomethyltin trichloride (MMT) and dimethyltin dichloride (DMT) on various neuronal ion channels heterologously expressed in Xenopus oocytes and on synaptic transmission in hippocampal slices of young (14-21 days old) and adult (2-4 months old) rats. The Xenopus oocyte expression system was chosen to allow direct assessment of the effects of MMT and DMT both on glutamate receptors sensitive to AMPA and NMDA and on various voltage-operated potassium and sodium channels. Hippocampal slices were used to analyze the effects of MMT and DMT on synaptic potentials generated by the important excitatory Schaffer collateral-CA1 synapse. In general, MMT and DMT were found to have no effect either on voltage-operated sodium and potassium channels or on the metabotropic glutamate receptor but they did differentially affect the functions of ionotropic glutamate receptors and glutamatergic synaptic transmission. MMT (100 microM) significantly reduced NMDA-mediated ion currents by up to 32%, but had no effect on ion currents through AMPA receptors. In slices of adult rats, MMT had no effect on the amplitudes of evoked fEPSPs and brought about a 35% reduction in the LTP amplitudes. In contrast, in slices of young rats MMT evoked a reversible 30% increase in the amplitudes of fEPSPs but had no effect on LTP induction. DMT (100 microM) reduced ion currents through NMDA-receptor ion channels by up to 29% and those through AMPA-receptor ion channels by up to 7%. In hippocampal slices 100 microM DMT reduced the amplitudes of fEPSPs (adults: 50%; young rats: 70%) and LTP (adults: 40%; young rats: 55%). Neither of the organotins affected the paired-pulse facilitation at this synapse, indicating that the organotins exert their effects at the postsynaptic site. The action of MMT and DMT may contribute to the organotin-induced impairment of behavior patterns in connection with learning and memory.
本研究的目的是调查三氯化一甲基锡（MMT）和二氯化二甲基锡（DMT）对非洲爪蟾卵母细胞中异源表达的各种神经元离子通道以及幼年（14 - 21日龄）和成年（2 - 4月龄）大鼠海马切片中突触传递的影响。选择非洲爪蟾卵母细胞表达系统是为了直接评估MMT和DMT对AMPA和NMDA敏感的谷氨酸受体以及各种电压门控钾通道和钠通道的影响。使用海马切片来分析MMT和DMT对重要的兴奋性谢弗侧支 - CA1突触产生的突触电位的影响。总体而言，发现MMT和DMT对电压门控钠通道和钾通道或代谢型谷氨酸受体均无影响，但它们确实对离子型谷氨酸受体的功能和谷氨酸能突触传递有不同的影响。MMT（100微摩尔）可使NMDA介导的离子电流显著降低达32%，但对通过AMPA受体的离子电流无影响。在成年大鼠的切片中，MMT对诱发的场兴奋性突触后电位（fEPSP）的幅度无影响，但使长时程增强（LTP）幅度降低了35%。相比之下，在幼年大鼠的切片中，MMT使fEPSP的幅度可逆性增加30%，但对LTP诱导无影响。DMT（100微摩尔）使通过NMDA受体离子通道的离子电流降低达29%，使通过AMPA受体离子通道的离子电流降低达7%。在海马切片中，100微摩尔的DMT降低了fEPSP的幅度（成年：50%；幼年大鼠：70%）和LTP（成年：40%；幼年大鼠：55%）。这两种有机锡均不影响该突触处的双脉冲易化，表明有机锡在突触后位点发挥作用。MMT和DMT的作用可能导致有机锡诱导的与学习和记忆相关的行为模式受损。
