Heppner T J, Fiekers J F
Department of Anatomy and Neurobiology, College of Medicine, University of Vermont, Burlington 05405.
Neuropharmacology. 1991 Aug;30(8):843-54. doi: 10.1016/0028-3908(91)90118-u.
The effects of soman, sarin and VX were examined on ganglionic transmission through paravertebral chain ganglia of the bullfrog, Rana catesbeiana. Low frequency (0.1 Hz), short (2 sec) and long (10 sec) trains of preganglionic stimulation, after exposure to the agents, induced repetitive activity in the extracellularly recorded compound action potential. An irreversible transient depression was observed after exposure to the agents during the first second of short and long stimulus trains. Long stimulus trains of high frequency were required to produce a rundown in the amplitude of the compound action potential, whether recorded in the presence of each agent (10 microM) or following a wash with agent-free solution. The rundown of the compound action potential was use-dependent and not blocked or reversed by atropine (10 microM). Intracellular recordings, in the presence of either soman or VX, demonstrated (1) an increase in the amplitude of the residual excitatory postsynaptic potential or current evoked by synaptic stimulation, (2) an increase in the amplitude and duration of the acetylcholine-induced potential, (3) no increase in either the amplitude or duration of the carbachol-induced potential, (4) repetitive firing with orthodromic but not antidromic stimulation and (5) a concentration- and frequency-dependent depolarization of individual ganglion neurons with orthodromic stimulation which resulted in a decrease in the generation of action potentials. These results suggest that the agent-induced decrease in the compound action potential occurred as a consequence of activity-dependent depolarization of ganglion neurons, which occurs after inhibition of cholinesterase.
研究了梭曼、沙林和VX对牛蛙（Rana catesbeiana）椎旁链神经节神经节传递的影响。在暴露于这些药剂后，低频（0.1Hz）、短（2秒）和长（10秒）的节前刺激串，在细胞外记录的复合动作电位中诱发了重复活动。在短刺激串和长刺激串的第一秒内暴露于药剂后，观察到不可逆的短暂抑制。无论是在每种药剂（10μM）存在的情况下记录，还是在用无药剂溶液冲洗后记录，都需要高频长刺激串才能使复合动作电位的幅度降低。复合动作电位的降低是使用依赖性的，且不受阿托品（10μM）的阻断或逆转。在存在梭曼或VX的情况下进行细胞内记录，结果表明：（1）突触刺激诱发的残余兴奋性突触后电位或电流的幅度增加；（2）乙酰胆碱诱发电位的幅度和持续时间增加；（3）卡巴胆碱诱发电位的幅度和持续时间均未增加；（4）正向刺激而非逆向刺激可诱发重复放电；（5）正向刺激时，单个神经节神经元出现浓度和频率依赖性去极化，导致动作电位的产生减少。这些结果表明，药剂诱发的复合动作电位降低是神经节神经元活动依赖性去极化的结果，这种去极化发生在胆碱酯酶受到抑制之后。
