School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom.
Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13515-9. doi: 10.1073/pnas.1001695107. Epub 2010 Jul 12.
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-beta receptors. We present evidence that TGF-beta2 regulates QSpre at the NMJ. Application of TGF-beta2 to the rat diaphragm NMJ increased the postsynaptic response to both spontaneous and evoked release of acetylcholine, whereas antibodies to TGF-beta2 or its receptor had the converse effect. L-vesamicol and bafilomycin blocked the actions of TGF-beta2, indicating that TGF-beta2 acts by altering the extent of vesicular filling. Recordings of the postsynaptic currents from the diaphragm were consistent with TGF-beta2 having this presynaptic action and a lesser postsynaptic effect on input resistance. TGF-beta2 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-beta2 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.
从突触前末梢释放的神经递质的量是量子含量（囊泡数量）和突触前量子大小（QSpre，每个囊泡中的递质量）的乘积。QSpre 随突触的使用而变化，但它的调节机制还不太清楚。运动神经末梢在神经肌肉接头（NMJ）处含有 TGF-β 受体。我们提供的证据表明，TGF-β2 调节 NMJ 处的 QSpre。将 TGF-β2 应用于大鼠膈肌 NMJ 会增加对乙酰胆碱自发和诱发释放的突触后反应，而 TGF-β2 的抗体或其受体则有相反的作用。L-vesamicol 和 bafilomycin 阻断了 TGF-β2 的作用，表明 TGF-β2 通过改变囊泡填充的程度起作用。从膈肌记录的突触后电流与 TGF-β2 具有这种突触前作用以及对输入电阻的较小的突触后作用一致。TGF-β2 还通过阿托品敏感途径减少量子含量，表明这种变化是囊泡释放的胆碱能反馈的次要作用。因此，TGF-β2 在 NMJ 上的净作用是放大自发传递的突触后效应，并减少每次诱发刺激使用的囊泡数量，而不减少释放的乙酰胆碱量。
