RUN-DOWN OF NEUROMUSCULAR-TRANSMISSION DURING REPETITIVE NERVE ACTIVITY BY NICOTINIC ANTAGONISTS IS NOT DUE TO DESENSITIZATION OF THE POSTSYNAPTIC RECEPTOR
RUN-DOWN OF NEUROMUSCULAR-TRANSMISSION DURING REPETITIVE NERVE ACTIVITY BY NICOTINIC ANTAGONISTS IS NOT DUE TO DESENSITIZATION OF THE POSTSYNAPTIC RECEPTOR
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DOI：
10.1111/j.1476-5381.1991.tb12258.x
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发表时间：
1991-04-01
影响因子：
7.3
通讯作者：
CHANG, CC
中科院分区：
文献类型：
--
作者：
HONG, SJ;CHANG, CC
1在竞争性拮抗剂存在下，在小鼠膈神经-半横膈上研究了突触后乙酰胆碱受体的功能是否受到重复神经刺激的使用依赖性影响。2对于电生理实验，用合成的芋螺毒素固定制剂，其优先阻断肌肉Na通道，既不引起膜电位的去极化，抑制量子递质的释放，也不抑制烟碱受体功能。3高浓度的眼镜蛇毒素抑制间接抽搐和终板电位（e.p.ps），而不诱导收缩性的减弱或在10-100 Hz诱发的e.p.ps序列的下降。然而，尽管突触后受体阻滞减少，但毒素洗脱后加速了衰减和下降。一旦www.example.com的下降e.p.ps是由洗脱或低浓度的眼镜蛇毒素产生的，用高浓度的眼镜蛇毒素进一步抑制e. p. p.振幅并不能减弱e. p. p.下降。4由非常高浓度的筒箭毒碱（20 μ M）产生的破伤风减弱和e. p. p.序列的程度也小于在低100倍浓度下引起的程度，尽管抽搐的幅度和第一个e. p. p.被更迅速和显著地抑制。5筒箭毒碱，像眼镜蛇毒素一样，比e. p. p. p.更能抑制微型终板电位的幅度m.e.p.ps。6与在低浓度的任一烟碱拮抗剂存在下连续e. p. p.的陡降相反，在m.e.p.ps重复刺激期间观察到的www.example.com的振幅是均匀的，并且与刺激前的振幅没有不同。7结果表明，由烟碱拮抗剂诱导的e. p. p.减弱和强直消退是由于突触前受体的缓慢动力学阻断，并且证实e. p. p.减弱不是由突触后烟碱受体的使用依赖性失效产生的。突触前烟碱受体在正反馈或负反馈调节递质释放的作用进行了讨论。
1 Whether the function of the postsynaptic acetylcholine receptor is use-dependently affected by repetitive nerve stimulation in the presence of competitive antagonists was studied in the mouse phrenic nerve-hemidiaphragm preparation.2 For electrophysiological experiments, the preparation was immobilized by synthetic mu-conotoxin, which preferentially blocks muscular Na-channels causing neither depolarization of the membrane potential, inhibition of quantal transmitter release, nor depression of nicotinic receptor function.3 High concentrations of cobratoxin depressed indirect twitches and endplate potentials (e.p.ps) without inducing waning of contractilities or run-down of trains of e.p.ps evoked at 10-100 Hz. However, waning and run-down were accelerated after washout of the toxin despite diminished postsynaptic receptor blockade. Once the run-down of e.p.ps was produced by washout or low concentrations of cobratoxin, further depression of e.p.p. amplitude with high concentrations of cobratoxin did not attenuate the e.p.p. run-down.4 The degrees of waning of tetanus and trains of e.p.ps produced by a very high concentration of tubocurarine (20-mu-M) were also less than that caused at a 100 fold lower concentration, albeit the amplitudes of twitches and the first e.p.p. were depressed more rapidly and markedly.5 Tubocurarine, like cobratoxin, depressed the amplitude of miniature endplate potentials (m.e.p.ps) more than e.p.ps.6 In contrast to the steepened run-down of successive e.p.ps in the presence of low concentrations of either nicotinic antagonists, the amplitude of m.e.p.ps observed during repetitive stimulation was uniform and was not different from that before stimulation.7 The results suggest that the e.p.p. run-down and tetanic fade induced by nicotinic antagonists are due to a slow kinetic blockade of presynaptic receptors and confirm that the e.p.p. run-down is not produced by a use-dependent failure of postsynaptic nicotinic receptors. The roles of the presynaptic nicotinic receptor in positive or negative feedback modulations of transmitter release are discussed.