Cooper G P, Suszkiw J B, Manalis R S
Neurotoxicology. 1984 Fall;5(3):247-66.
The acute effects of Pb++, Cd++ and Hg++ on synaptic transmission were studied on the in vitro sciatic nerve-sartorius muscle preparation of the frog, using electrophysiological techniques. Biochemical procedures were used to examine the effects of Pb++ and Cd++ on in vitro preparations of synaptosomes. In the electrophysiological studies Pb++ was shown to be a powerful competitive inhibitor of action potential-evoked release of acetylcholine (ACh) as judged by its depressant effects on the amplitude of endplate potentials (EPPs). The dissociation constant between Pb++ and the presynaptic Ca++ receptor is about 1 microM. Pb++ also increases spontaneous transmitter release as determined by the frequency of miniature endplate potentials (MEPPs). The increase in MEPP frequency is assumed to be due to an intracellular action of Pb++ to reduce the ability of nerve terminal organelles to buffer Ca++ and thereby, increases the intracellular concentration of Ca++. Cd++ also blocks evoked ACh release by a competitive inhibitory mechanism which appears similar to that for Pb++. The dissociation constant for Cd++ is about 2.8 microM. In contrast to Pb++, Cd++, does not increase resting MEPP frequency. Hg++ is unique in that it first causes an increase in evoked ACh release and then a sudden and complete blockade; the MEPP frequency follows a similar time course. The mechanism underlying these effects of Hg++ is uncertain. In rat brain synaptosomes, Pb++ and Cd++ competitively inhibit the K+-stimulated influx of 45Ca++. The dissociation constants for the interaction of Pb++ and Cd++ with Ca++ channels is 1.1 microM and 2.2 microM respectively. These data strongly support the idea that the electrophysiological effects of Pb++ and Cd++ on the EPP are due to a reduction of voltage-gated Ca++ entry into presynaptic nerve terminals.
采用电生理技术，在青蛙坐骨神经 - 缝匠肌体外制备标本上研究了Pb++、Cd++和Hg++对突触传递的急性影响。运用生化方法检测了Pb++和Cd++对突触体体外制备标本的影响。在电生理研究中，根据Pb++对终板电位（EPP）幅度的抑制作用判断，它是动作电位诱发的乙酰胆碱（ACh）释放的强效竞争性抑制剂。Pb++与突触前Ca++受体之间的解离常数约为1微摩尔。Pb++还会增加微小终板电位（MEPP）的频率，从而增加自发性递质释放。MEPP频率的增加被认为是由于Pb++的细胞内作用降低了神经末梢细胞器缓冲Ca++的能力，进而增加了细胞内Ca++的浓度。Cd++也通过类似Pb++的竞争性抑制机制阻断诱发的ACh释放。Cd++的解离常数约为2.8微摩尔。与Pb++不同，Cd++不会增加静息时的MEPP频率。Hg++的独特之处在于，它首先会导致诱发的ACh释放增加，然后突然完全阻断；MEPP频率也呈现类似的时间进程。Hg++产生这些效应的潜在机制尚不确定。在大鼠脑突触体中，Pb++和Cd++竞争性抑制K+刺激的45Ca++内流。Pb++和Cd++与Ca++通道相互作用的解离常数分别为1.1微摩尔和2.2微摩尔。这些数据有力地支持了以下观点：Pb++和Cd++对EPP的电生理效应是由于电压门控Ca++进入突触前神经末梢减少所致。
