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神经营养因子对神经肌肉接头传递的调制作用

詹文志, Mantilla C B, Sieck G C

梅佑医院麻醉、生理和生物物理学系.美国明尼苏达州罗切斯特 55905

摘要

运动单位由运动神经元及其支配的肌纤维组成。神经肌肉接头(NMJ)传递受到严密的调节,因而能和运动单位的活动协调一致。在NMJ,神经调制物质的释放与运动单位的活动有关,并能决定突触传递的效能。脑源性神经营养因子(BDNF)和神经营养因子4(NT-4)由运动神经末梢和肌纤维产生。肌肉释放营养因子受肌肉活动调节。在NMJ,BDNF和NT-4通过激活酪氨酸激酶B受体(TrkB),能加强自发性和诱导性的突触活动。突触前Ca~(2+)量的迅速增加或突触胞吐过程的易化,都能增加突触囊泡的释放,从而改善NMJ的突触传递。事实上,BDNF能促进突触前细胞内Ca~(2+)的释放,TrkB的激活也能通过有丝分裂活化蛋白激酶,引起突触素I(synapsin I)的磷酸化,进而增加可释放的突触囊泡的数量。在NMJ,神经营养因子还能通过影响神经调节素(neuregulin)或其他神经源性调制物质的局部释放,对接头传递进行调节。该文对近年来在NMJ突触传递的调节,运动单位的NMJ特性以及神经营养因子对突触传递效能的影响等方面的研究进展做一综述。

关键词： 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

Regulation of neuromuscular transmission by neurotrophins

Zhan Wenzhi, Mantilla C B, Sieck G C

Department of Anesthesiology and Physiology and Biophysics,Mayo Clinic and Foundation Rochester,MN 55905

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 Ca~(2+) transients or facilitated vesicular exocytosis. In fact, BDNF potentiates intracellular Ca~(2+) release presynaptically and BDNF-induced TrkB activation also results in phosphorylation of synapsin I via mitoen 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.

Key words: Brain-derived neurotrophic factor;Diaphragm muscle;Neuromuscular transmission ailure;Neurotrophin-4;Spinal cord injury synaptic efficacy;Synaptic vesicles tyrosine kinase receptor B;;

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引用本文：

詹文志, Mantilla C B, Sieck G C. 神经营养因子对神经肌肉接头传递的调制作用[J]. 生理学报 2003; 55 (6): .

Zhan Wenzhi, Mantilla C B, Sieck G C. Regulation of neuromuscular transmission by neurotrophins. Acta Physiol Sin 2003; 55 (6): (in Chinese with English abstract).