权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

DIAPHRAGM NEUROMUSCULAR TRANSMISSION: HYPOXIA & MATURITY

隔膜神经肌肉传输：缺氧

基本信息

批准号：
6526995
负责人：
Alia R Bazzy-Asaad
金额：
$ 20.17万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-07-01 至 2004-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6526995
关键词：
action potentials age difference calcium channel calcium channel blockers developmental neurobiology diaphragm hypoxia immunocytochemistry laboratory rat mature animal motor neurons neuromuscular transmission newborn animals phrenic nerve synapses

项目摘要

Respiratory failure is a major cause of morbidity in the newborn period. Evidence from our work and that of others suggests that in this age group diaphragmatic fatigue contributes to this failure, and that neuromuscular transmission (NMT) is an important site of failure. Based on recent data from our laboratory the probable mechanism underlying NMT failure is inadequate neurotransmitter. Although calcium is known to play a pivotal in transmitter release, little is known regarding the maturation of this process with development. Also, little is known regarding how the hypoxia that is associated with respiratory failure modulates NMT in this age group. Hence we hypothesize that: 1) NMT failure is secondary to presynaptic mechanisms at the motor nerve terminal. Ca2+ plays an important role in the development of NMT failure because of structural and/or functional immaturity of specific subtypes of Ca2+ channels in the presynaptic nerve terminal. This will be tested in the isolated rat diaphragm a) using electrophysiological techniques to assess transmitter release in the presence of blockers of Ca2+ channel subtypes; and b) morphologically assessing Ca2+ channel subtypes using immunocytochemistry and molecular techniques. 2) Chronic hypoxia delays the maturation of the NM junction. This is associated with delayed functional maturity of the synapse and decreased synaptic efficacy. This will be tested by comparing the: a) morphology; b) force response; c) action potentials failures; d) quantal content and safety factor; and e) Ca2+ channels of diaphragms of rats raised in chronic hypoxia to control littermates at several time points during the first postnatal month. We believe that these studies will provide a better understanding of the mechanisms underlying diaphragmatic fatigue and respiratory failure in the newborn.

呼吸衰竭是新生儿期发病的主要原因。我们的工作和其他人的工作的证据表明，在这个年龄组中，运动性疲劳有助于这种失败，神经肌肉传递（NMT）是一个重要的网站失败。根据我们实验室最近的数据，NMT失败的可能机制是神经递质不足。虽然钙在递质释放中起着关键作用，但对这一过程的成熟与发育知之甚少。此外，关于与呼吸衰竭相关的缺氧如何调节该年龄组的NMT知之甚少。因此，我们推测：1）NMT的失败是继发于运动神经末梢的突触前机制。由于突触前神经末梢中特定亚型的Ca 2+通道的结构和/或功能不成熟，Ca 2+在NMT失败的发展中起重要作用。这将在分离的大鼠膈肌中进行测试，a）使用电生理学技术评估在存在Ca 2+通道亚型阻断剂的情况下的递质释放;和B）使用免疫细胞化学和分子技术从形态学上评估Ca 2+通道亚型。 2)慢性缺氧延迟NM连接的成熟。这与突触的功能成熟延迟和突触功效降低有关。这将通过比较出生后第一个月内几个时间点在慢性缺氧条件下饲养的大鼠与对照同窝仔大鼠的横膈膜的以下各项进行检测：a）形态学; B）力反应; c）动作电位失败; d）量子含量和安全系数;以及e）Ca 2+通道。我们相信，这些研究将提供一个更好地了解新生儿的呼吸疲劳和呼吸衰竭的机制。