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RESEARCH PRODUCT
Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4
Antonino CasabonaNatale BelluardoCarlos F. IbáñezGiusepa MudóJoseph D. BrutonHåkan WesterbladFrancesca GrassiGiuseppina CanigliaOrnella Pastorissubject
End-plate potentialNeuromuscular JunctionElectromyographyBiologyNeuromuscular junctionCellular and Molecular NeuroscienceMicePostsynaptic potentialmedicineAnimalsReceptors CholinergicNerve Growth FactorsMuscle SkeletalMolecular BiologyAcetylcholine receptorMice KnockoutMotor Neuronsmedicine.diagnostic_testMuscle fatigueElectromyographyAge FactorsLong-term potentiationneuromuscular junction; neurotrophin-4; synaptic transmissionCell Biologymedicine.anatomical_structureMuscle Fibers Slow-TwitchMuscle FatigueAcetylcholinesteraseTetanic stimulationNeuroscienceMuscle Contractiondescription
Neurotrophin-4 (NT-4) is produced by slow muscle fibers in an activity-dependent manner and promotes growth and remodeling of adult motorneuron innervation. However, both muscle fibers and motor neurons express NT-4 receptors, suggesting bidirectional NT-4 signaling at the neuromuscular junction. Mice lacking NT-4 displayed enlarged and fragmented neuromuscular junctions with disassembled postsynaptic acetylcholine receptor (AChR) clusters, reduced AChR binding, and acetylcholinesterase activity. Electromyographic responses, posttetanic potentiation, and action potential amplitude were also significantly reduced in muscle fibers from NT-4 knock-out mice. Slow-twitch soleus muscles from these mice fatigued twice as rapidly as those from wild-type mice during repeated tetanic stimulation. Thus, muscle-derived NT-4 is required for maintenance of postsynaptic AChR regions, normal muscular electrophysiological responses, and resistance to muscle fatigue. This neurotrophin may therefore be a key component of an activity-dependent feedback mechanism regulating maintenance of neuromuscular connections and muscular performance.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2001-01-01 |