在不均匀牵拉的离体大鼠膈肌标本上梭曼的突触前和突触后作用

在离体大鼠膈肌上制备了一种不均匀牵拉肌肉以制动,便于用微电极记录终板电位(EPP)的标本(INSMP),避免了常规制动方法带来的制动药物、台氏液Ca~(2+),Mg~(2+)浓度改变或钳压肌肉导致膜电位(MP)下降的种种干扰。INSMP的MP和小终板电位(MEPP)正常,EPP幅度高达30mV以上,是研究药物对接头作用的较好标本。在INSMP上,梭曼(5.5μM)使MEPP频率加快,串刺激(50Hz)诱发的平均串EPPs幅度及其平均ACh 量子含量减少80％和77％。小剂量三碘季铵酚和六烃季铵可部分对抗梭曼的作用。梭曼引起强直收缩抑制主要原因为终板区蓄积的ACh作用于突触前N受体、负反馈地抑制ACh 量子释放;次要原因为作用突触后N受体、使其对ACh敏感性降低。

The presynaptic and postsynaptic effect of somanin isolated non-uniform stretched musclepreparation(INSMP) of rat diaphragm

The mechanism of tetanic fade evoked by repetitive stimulation after exposure to anticholinesterace is still not well known. We are interested in its presynap tic mechanism. In order to record the EPPs by microelectrode in the condition of "free drug", we have developed an isolated non uniform stretched muscle preparatiop(IN SMP) of rat diaphragm by pinning it on a plexiglas plate. The membrane potentials of INSMP could be maintained above-65mV and the MEPP and EPP of high amplitude (30-36) mV) could be simultaneously recorded from the same microelctrode in the intermediate zone between the contractile and noncontractile areas evoked by indirect stimulation. Stretching the muscle did not affect the frequency and amplitude of MEPP and membrane-potential. These results show that INSMP is more suitable than dTc or high Mg2+ treated preparations for observing the effects of drugs on the neuro- muscular transmission.In INSMP after exposure to soman (5.5 (μM), the frequency of MEPP was increased to 310 % of normal, the mean amplitude of EPPs (50 Hz) was significantly decreased about 80 % and their mean quantal contents were depressed about 84% of the control. These changes can result in tetanic fade of diaphragm. Pretreatment with small doses of gallamine (50μM) or hexamethonium (0.3 mM), which had no influences on EPPs, could partially prevent the effect of soman on EPPs and their mean quantal contents.It was observed that in INSMP the MEP Ps could still be recorded between obviously depressed trains of EPPs evoked by 50 Hz stimulation in presence of soman. Theamplitude of acetylcholine potential (AChP), evoked by microiontophoretically released ACh immediately after the last EPP of atrain of EPPs, was reduced about 30 % as compared with AChP before a train of EPPs. These indicate that after soman the ACh, released from the nerve terminals by a train of indirect stimulation, can depress the sensitivity of postsynaptic ACh receptor in about 30 % and the significant decrease of the mean amplitude of EPPs after soman is due to mainly the decrease of presynaptic ACh quantal release by a negative feedback pathway.