Open AccessTGF-β2 alters the characteristics of the neuromuscular junction by regulating presynaptic quantal size
Author(s) -
Sitt Wai Fong,
Ian S. McLennan,
Andrew R. McIntyre,
Jayne Reid,
K. I. J. Shennan,
Guy S. Bewick
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1001695107
Subject(s) - postsynaptic potential , neuromuscular junction , acetylcholine , acetylcholine receptor , neurotransmission , biology , neurotransmitter , cholinergic , synaptic vesicle , inhibitory postsynaptic potential , neuromuscular transmission , neuroscience , excitatory postsynaptic potential , microbiology and biotechnology , receptor , chemistry , vesicle , endocrinology , biochemistry , central nervous system , membrane
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.