POSTNATAL DEVELOPMENTAL CHANGES OF AIRWAY SMOOTH MUSCLE

肺部疾病在新生儿期相对常见，特别是在早产儿中。支气管扩张剂治疗对婴幼儿慢性肺部疾病是有益的，这表明在这种普遍和严重的疾病中，气道平滑肌起着重要的作用。众所周知，胎儿和成人的呼吸道平滑肌的细胞功能有很大的不同，我们认为这些情况之间的过渡在出生后会延长一段时间。我们在猪模型上获得的数据表明，新生动物和成年动物的气管平滑肌在以下方面存在显著差异：1)对K+通道阻滞剂的收缩敏感性；2)细胞内游离钙浓度与张力的关系。我们的结果与一般的假设是一致的，即呼吸道平滑肌经历了从阶段到紧张性肌肉的转变，从出生前开始，但一直持续到儿童早期。残留的时相特征可能易发生支气管痉挛。因此，我们建议表征从猪和人获得的呼吸道平滑肌的钙稳态随年龄的变化。我们的目标是确定涉及生后收缩钙敏感性变化的发育机制的细胞学基础，并表征猪和人出生后钙稳态变化的时间过程。这些研究将提供与年龄相关的呼吸道功能变化的信息，这对于理解儿童早期独特的肺部疾病非常重要。我们的结果可能会为治疗或预防婴儿期支气管痉挛提供更有效的方法。

Pulmonary disease is relatively common in the neonatal period, especially in those born prematurely. Bronchodilator therapy is beneficial in chronic lung diseases of infancy, suggesting an important role of airway smooth muscle in this prevalent and serious condition. It is known that the cellular function of airway smooth muscle is quite different in the fetus than in the adult and we suggest that the transition between these conditions extends for some time after birth. We have obtained data in a pig model which demonstrate striking differences between tracheal smooth muscles of newborn and adult animals with regard to 1) contractile sensitivity to K+ channel blockers and 2) the relationship between intracellular free Ca2+ concentration and tension. Our results are consistent with the general hypothesis that airway smooth muscle undergoes a transition from a phasic to a tonic muscle, beginning before birth but continuing into early childhood. Residual phasic characteristics may predispose to bronchospasm. We therefore proposed to characterize changes with age in Ca2+ homeostasis of airway smooth muscles obtained from pigs and humans. Our aims are to determine the cellular basis for developmental mechanisms involved in postnatal changes in contractile Ca2+ sensitivity, and to characterize the time course of postnatal changes in Ca2+ homeostasis in both pigs and humans. These studies will provide information regarding age-related changes in airway function that is important for understanding the unique pulmonary diseases of early childhood. Our results may suggest more effective approaches to the therapy or prevention of bronchospastic conditions of infancy.