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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >TGF-β2 alters the characteristics of the neuromuscular junction by regulating presynaptic quantal size
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TGF-β2 alters the characteristics of the neuromuscular junction by regulating presynaptic quantal size

机译:TGF-β2通过调节突触前的数量大小来改变神经肌肉接头的特征

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摘要

The amount of neurotransmitter released from a presynaptic terminal is the product of the quantal content (number of vesicles) and the presynaptic quantal size (QSpre, amount of transmitter per vesicle). QSpre varies with synaptic use, but its regulation is poorly understood. The motor nerve terminals at the neuromuscular junction (NMJ) contain TGF-β receptors. We present evidence that TGF-β2 regulates QSpre at the NMJ. Application of TGF-β2 to the rat diaphragm NMJ increased the postsynaptic response to both spontaneous and evoked release of acetylcholine, whereas antibodies to TGF-β2 or its receptor had the converse effect. L-vesamicol and bafilomycin blocked the actions of TGF-β2, indicating that TGF-β2 acts by altering the extent of vesicular filling. Recordings of the postsynaptic currents from the diaphragm were consistent with TGF-β2 having this presynaptic action and a lesser postsynaptic effect on input resistance. TGF-β2 also decreased quantal content by an atropine-sensitive pathway, indicating that this change is secondary to cholinergic feedback on vesicular release. Consequently, the net actions of TGF-β2 at the. NMJ were to amplify the postsynaptic effects of spontaneous transmission and to diminish the number of vesicles used per evoked stimulus, without diminishing the amount of acetylcholine released.
机译:从突触前末端释放的神经递质的量是定量含量(囊泡的数量)和突触前定量大小(QSpre,每个囊泡的递质的量)的乘积。 QSpre随突触的使用而变化,但对其调节了解甚少。神经肌肉接头(NMJ)的运动神经末梢含有TGF-β受体。我们提供证据表明,TGF-β2在NMJ上调节QSpre。将TGF-β2应用于大鼠diaphragm肌NMJ可增加对乙酰胆碱的自发和诱发释放的突触后反应,而针对TGF-β2或其受体的抗体则具有相反的作用。 L-维他命醇和巴氟霉素阻断了TGF-β2的作用,表明TGF-β2通过改变囊泡充盈程度起作用。来自隔膜的突触后电流的记录与具有这种突触前作用并且对输入电阻的较小的突触后作用的TGF-β2一致。 TGF-β2还通过阿托品敏感途径降低了定量含量,表明该变化是囊泡释放后胆碱能反馈的继发性变化。因此,TGF-β2的净作用。 NMJ可以增强自发传递的突触后作用,并减少每个诱发刺激使用的囊泡数量,而不会减少乙酰胆碱的释放量。

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