Muscle Nerve 2016 Apr 01;534:593-7. doi: 10.1002/mus.24793.

Brain-derived neurotrophic factor inhibits neuromuscular junction maturation mediated by inTracellular Ca(2+) and Ca(2+)/calmodulin-dependent kinase.

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Brain-derived neurotrophic factor (BDNF) inhibits neuromuscular junction (NMJ) maturation. In this study we investigated the underlying molecular mechanisms of this process. We used a patch-clamp technique to measure spontaneous synaptic currents (SSCs) from innervated muscle cells in Xenopus nerve-muscle cocultures. 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. 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.

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Species referenced: Xenopus
Genes referenced: adm bdnf