Neurotrophins improve neuromuscular transmission in the adult rat diaphragm

• Published in: Muscle & nerve Vol. 29; no. 3; pp. 381 - 386
• Main Authors: Mantilla, Carlos B., Zhan, Wen-Zhi, Sieck, Gary C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2004; Wiley
• Subjects: Animals; Biological and medical sciences; Brain-Derived Neurotrophic Factor - pharmacology; Carbazoles - pharmacology; Diaphragm - innervation; Diaphragm - physiology; Electric Stimulation; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Indole Alkaloids; Male; motor unit; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle Fatigue - drug effects; Muscle Fatigue - physiology; Nerve Growth Factors - pharmacology; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; neuromuscular transmission failure; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; phrenic motoneurons; plasticity; Rats; Rats, Sprague-Dawley; Receptor, trkB - antagonists & inhibitors; Receptor, trkB - metabolism; synaptic efficacy; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; ventilation; Vertebrates: nervous system and sense organs; Neurotrophin; tropomyosin-related Kinase receptor motor unit; Rat; Rodentia; synaptic efficacy ventilation; phrenic motoneurons; plasticity; Motor neuron; trk receptor; Muscular fiber; Striated muscle; Neuromuscular transmission; Neuromuscular junction; Vertebrata; Mammalia; Phrenic nerve; Synaptic plasticity; Diaphragm; Brain derived neurotrophic factor; neuromuscular transmission failure; Respiration
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.10558

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. Muscle Nerve 29: 381–386, 2004