Neurotrophins improve neuromuscular transmission in the adult rat diaphragm.
Neurotrophins modulate acute and sustained synaptic plasticity. In cultured Xenopus laevis neuromuscular junctions, neurotrophins improve neuromuscular transmission. Whether this influence exists at the mammalian neuromuscular junction is unknown. We hypothesized that neurotrophins improve neuromuscular transmission at neuromuscular junctions of adult rat diaphragm muscle fibers. A diaphragm muscle-phrenic nerve preparation was used to determine the effects of brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4) and K252a [tyrosine kinase (Trk) receptor inhibitor] on the extent of neuromuscular transmission failure induced by repetitive nerve stimulation. We found significant enhancement of neuromuscular transmission with BDNF or NT-4 treatment, whereas K252a treatment worsened neuromuscular transmission. In contrast, diaphragm muscle contractile and fatigue properties were unaffected by neurotrophin or K252a treatment. These results demonstrate that BDNF and NT-4 improve synaptic transmission in the adult rat diaphragm muscle, likely in a Trk-dependent fashion. Neurotrophins may constitute a novel therapeutic target to improve neuromuscular function in the diaphragm.
Department of Anesthesiology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Carlos B
CB
Mantilla
Wen-Zhi
WZ
Zhan
Gary C
GC
Sieck
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D003964:Diaphragm / Q000294:innervation / Q000502:physiology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D026121:Indole Alkaloids; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; C049985:staurosporine aglycone; D020813:Receptor, trkB; C073922:neurotrophin 4