PHYSIOLOGY AND PATHOPHYSIOLOGY OF ESOPHAGEAL MOTILITY

这项研究建议的主要目的是：(1)阐明 (A)食道蠕动和(B)下食道括约肌的生理学 (1)语调和松弛；(2)辨别语气的性质 参与食道反射活动的神经递质；(3)探索 食管体和LES的药理学；以及(4)达到 通过补充它们来合成结构-功能关系 通过形态调查进行研究。这些在动物身上的研究 模型将扩展到在手术中获得的病变组织 食道疾病患者。 我们将使用一些不同的体内和体外系统来记录 间接(吸气电极)和直接(单一电极)的膜电位 细胞内)方法，从而了解神经的本质 无论是在完好的动物身上还是在肌肉条上都有反射。这些研究 也将延伸到肌间神经丛的形态和形态计量学， 使用我们最近开发的快速无银方法和我们的技术 神经节细胞隔离。一种免疫细胞化学方法将提供有价值的 组织生理学见解以补充形态学发现。 神经节细胞分离也将用于研究超微结构 人的肌间神经丛的扫描和透射电子显微镜观察 食道的不同部分。形态和生理 因此，将建立食道功能的神经控制的相关性。 这些研究将促进我们对食道生理学的理解 食道运动障碍的运动与病理生理学。这 理解可能会为理性对待这些问题提供途径 精神错乱。此外，从这些对食道的研究中学到的教训 可能在生理学和病理生理学方面有更广泛的意义 自主神经系统，尤指胃肠道的。

The major objectives of this research proposal are: (1) to elucidate the physiology of (a) esophageal peristalsis and (b) lower esophageal sphincter (LES) tone and relaxation; (2) to identify the nature of the neurotransmitters involved in esophageal reflex activities; (3) to explore the pharmacology of esophageal body and LES; and (4) to arrive at a synthesis of structure-function relationships by complementing these studies with morphological investigations. These studies in the animal model will be extended to diseased tissues obtained at surgery from patients with esophageal disorders. We will use a number of different in vivo and in vitro systems to record membrane potentials by indirect (suction electrodes) and direct (single cell intracellular) methods, so as to learn about the nature of the neural reflexes in both intact animals as well as in muscle strips. These studies will also extend to the morphology and morphometry of the myenteric plexus, using our recently-developed rapid non-silver method and our technique of ganglionic isolation. An immunocytochemical approach will provide valuable histophysiological insights to supplement morphological findings. Ganglionic isolation will also be used to investigate ultrastructure with scanning and transmission electron microscopy of the myenteric plexus from various segments of the esophagus. Morphologic and physiologic correlations of neural control of esophageal function will thus be made. These studies will advance our understading of the physiology of esophageal motility and the pathophysiology of esophageal motor disorders. This understanding may provide avenues for rational treatment of these disorders. Moreover, lessons learned from these studies of the esophagus may have wider implications in physiology and pathophysiology of the autonomic nervous system, particularly that of the gastrointestinal tract.