title: Brain-derived neurotrophic factor inhibits neuromuscular junction maturation mediated by inTracellular Ca(2+) and Ca(2+)/calmodulin-dependent kinase.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) inhibits neuromuscular junction (NMJ) maturation. In this study we investigated the underlying molecular mechanisms of this process.
  
  
  METHODS
  We used a patch-clamp technique to measure spontaneous synaptic currents (SSCs) from innervated muscle cells in Xenopus nerve-muscle cocultures.
  
  
  RESULTS
  In the presence of Ca(2+)/calmodulin-dependent kinase (CaMK) inhibitor KN93, SSC amplitude (226.3 ± 26.5 pA), frequency (30.9 ± 10.1 events/min), and percentage of bell-shaped amplitude distributions (47.1%) were reversed to control levels (286.7 ± 48.2 pA, 26.2 ± 5.8 events/min, and 47.1%, respectively). Depletion of intracellular Ca(2+) by BAPTA-AM or thapsigargin had similar reversal effects to KN93. In addition, cotreatment with both 2-APB (IP3 receptor inhibitor) and TMB-8 (ryanodine receptor inhibitor) also reversed the inhibitory effects of BDNF, as shown by the physiological parameters.
  
  
  CONCLUSIONS
  CaMK mediates the inhibitory effects of BDNF on NMJ maturation. Ca(2+) released from intracellular stores through either IP3 receptors or ryanodine receptors regulates neurotrophic actions on NMJ maturation.
authors.affiliation: Peking University Health Science Center, Mailbox 045, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.|Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Xiwan Albert
authors.initials: XA
authors.lastname: Jin
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D009924:Organ Culture Techniques; D014981:Xenopus
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium
keywords: Ca2+; Ca2+/calmodulin-dependent kinase; IP3 receptor; brain-derived neurotrophic factor; ryanodine receptor