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Regulation of neuromuscular transmission by neurotrophins

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Author:: No author available

Journal Title:: ACTA PHYSIOLOGICA SINICA

Issue:: 6

DOI:: 10.3321/j.issn:0371-0874.2003.06.001

Key Word:: 脑源性神经营养因子;膈肌;神经肌肉传导阻滞;神经营养因子4;脊髓损伤;突触效能;突触囊泡;酪氨酸激酶B受体;brain-derived neurotrophic factor;diaphragm muscle;neuromuscular transmission failure;neurotrophin-4;spinal cord injury;synaptic efficacy;synaptic vesicles;tyrosine kinase receptor B

Abstract： Motor units comprise a motoneuron and the muscle fibers it innervates. Neuromuscular transmission is tightly regulated to match the activity of individual motor units. Activity-dependent release of neuromodulators at the neuromuscular junction (NMJ) determines the efficacy of transmission. The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) are produced by motoneurons and muscle fibers, and their release by skeletal muscle is regulated by muscle activity. BDNF and NT-4 enhance both spontaneous and evoked synaptic transmission at NMJs via activation of the tyrosine kinase receptor B (TrkB). Improvements in neuromuscular transmission may result from increased release of synaptic vesicles, either by presynaptic alterations in Ca2 + transients or facilitated vesicular exocytosis. In fact, BDNF potentiates intracellular Ca2 + release presynaptically and BDNF-induced TrkB activation also results in phosphorylation of synapsin Ⅰ via mitogen activated protein kinase, which increases the number of synaptic vesicles available for release. Neurotrophins may also regulate synaptic transmission at the NMJ by increasing local release of neuregulin or other nerve-derived modulators. We review recent studies on the regulation of neuromuscular transmission, the motor unit-specific properties of NMJs and the effects of neurotrophins on synaptic efficacy at the NMJ.

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