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Neuregulin 1 modulates neuromuscular transmission in diaphragm muscle during early postnatal development
Author(s) -
Ermilov Leonid G,
Mantilla Carlos B,
Zhan WenZhi,
Sieck Gary C
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.653.9
Diaphragm muscle (DIAm) activation during ventilatory behaviors changes postnatally being near maximal at birth and submaximal later on. The molecular determinants of this transition are unknown. Neuregulin‐1 (NRG1) induces expression of acetylcholine (ACh) receptors at developing neuromuscular junctions (NMJ), and increases ACh‐induced currents in cultured hippocampal neurons. We hypothesized that NRG1 modulates neuromuscular transmission at DIAm NMJs during early postnatal development. Neuromuscular transmission failure (NMTF) was assessed in DIAm‐phrenic nerve preparations from male Sprague‐Dawley rats as the difference in force developed during repetitive phrenic nerve stimulation (0.2 ms pulses, 40 Hz, 330‐ms trains for 2 min) and the force developed by intermittent (every 15 s) direct DIAm stimulation (two trains of 2 ms pulses, 40 Hz, 330‐ms). Exogenous NRG1 (recombinant human heregulin β177–244; 40 nM) significantly improved neuromuscular transmission in 0‐ and 7‐day old rats, but not in 14‐day old rats. The NRG/ErbB signaling inhibitors AG879 and AG1478 eliminated NRG1's effect. These results indicate that NRG1 has important synaptic effects during early postnatal development and may thus contribute to the near maximal activation of DIAm motor units necessary during ventilatory behaviors. Supported by NIH grant AR051173.