Yuan Y, Atchison W D
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, USA.
J Pharmacol Exp Ther. 1995 Dec;275(3):1308-16.
To explore the mechanisms by which methylmercury (MeHg) blocks central synaptic transmission, intracellular recordings of action potentials and resting membrane potentials were made in CA1 neurons of rat hippocampal slices. At 4 to 100 microM, MeHg blocked action potentials in a concentration- and time-dependent manner. MeHg also depolarized Ca1 neuronal membranes. However, this effect occurred more slowly than block of action potentials because the resting membrane potentials remained unchanged when threshold stimulation-evoked action potentials were blocked. Thus, MeHg may initially alter the threshold level of neuronal membrane excitability and subsequently depolarize the membrane leading to block of synaptic transmission. To identify potential sites of action of MeHg, effects of MeHg on the responses of CA1 neurons to orthodromic stimulation of Schaffer collaterals, antidromic stimulation of the alveus, direct injection of current at cell soma and iontophoretic application of glutamate were compared. At 20 and 100 microM, MeHg blocked action potentials evoked by stimulation of Schaffer collaterals and by current injection at the cell soma at similar times. In contrast, action potentials evoked by stimulation of the alveus were blocked more rapidly by 100 microM MeHg than were action potentials evoked by current injection at CA1 neuronal soma. MeHg also blocked the responses of CA1 neurons to iontophoresis of glutamate, but time to block of these responses was slower than block of the corresponding orthodromically-evoked responses by stimulation of Schaffer collaterals. Compared to excitatory postsynaptic potentials, inhibitory postsynaptic potentials appeared to be more sensitive to MeHg, because block of inhibitory postsynaptic potentials occurred before block of excitatory postsynaptic potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
为探究甲基汞（MeHg）阻断中枢突触传递的机制，在大鼠海马脑片的CA1神经元中进行了动作电位和静息膜电位的细胞内记录。在4至100微摩尔浓度下，MeHg以浓度和时间依赖性方式阻断动作电位。MeHg还使CA1神经元膜去极化。然而，这种效应比动作电位的阻断发生得更慢，因为当阈值刺激诱发的动作电位被阻断时，静息膜电位保持不变。因此，MeHg可能最初改变神经元膜兴奋性的阈值水平，随后使膜去极化，导致突触传递阻断。为确定MeHg的潜在作用位点，比较了MeHg对CA1神经元对Schaffer侧支的顺向刺激、海马槽的逆向刺激、细胞体直接注入电流以及谷氨酸离子导入的反应的影响。在20和100微摩尔浓度下，MeHg在相似时间阻断了由Schaffer侧支刺激和细胞体电流注入诱发的动作电位。相比之下，100微摩尔MeHg对海马槽刺激诱发的动作电位的阻断比CA1神经元细胞体电流注入诱发的动作电位更快。MeHg还阻断了CA1神经元对谷氨酸离子导入的反应，但阻断这些反应的时间比Schaffer侧支刺激相应顺向诱发反应的阻断要慢。与兴奋性突触后电位相比，抑制性突触后电位似乎对MeHg更敏感，因为抑制性突触后电位的阻断在兴奋性突触后电位阻断之前发生。（摘要截短于250字）
