PHYSIOLOGY AND PATHOPHYSIOLOGY OF ESOPHAGEAL MOTILITY

描述：这些研究的总体目标是了解 血管内皮细胞质膜离子通道的作用 食道蠕动。一氧化氮是一种主要的神经递质，在 食道蠕动，但其平滑肌离子通道 活性是由NO介导的，目前还没有确定。初步数据 提示NO可调节钙刺激的氯化物的活性 电流(最近由PI确定)以产生其生理 对食道肌肉细胞的影响。一氧化氮还可能改变一种新的钙- PI所描述的在回肠肌细胞中激活的K通道。这个 PI还证明了NO供体的行为依赖于氧化还原 已生成NO状态。重要的初步数据表明，没有*是 内源性氮能神经递质的氧化还原形式。这样做的目的是 应用是检查硝普钠(一号)的作用 供体)、亚硝基(NO供体和可能的EDRF)和胺/NO 加合物(没有*像DNO这样的捐赠者)。将进行功能研究，以研究 细胞贴附和切除的膜片中的单通道电流。 整个细胞和穿孔的斑片电流将被研究以表征 通道电流、NO供体的作用和信号通路。 环行肌中通道蛋白的分子表达 用已发表的Ca-1的c DNA和序列进行原位杂交 氯离子和钙离子的小电导钾通道。一氧化氮对单个细胞的影响 将与氮能神经传递和生理学有关 微电极、力学研究与食道运动测量 在活体内。

DESCRIPTION: The overall objective of these studies is to understand the role of ion channels in the plasma membrane of smooth muscle cells in esophageal peristalsis. Nitric oxide is a major neurotransmitter in esophageal peristalsis, however the smooth muscle ion channel whose activity is mediated by NO has not been identified. Preliminary data suggest that NO modifies the activity of calcium-stimulated chloride currents (recently identified by the PI) to produce its physiological effects on esophageal muscle cells. NO may also alter a novel calcium- activated K channel that the PI has described in ilial muscle cells. The PI has also demonstrate that the actions of NO donors depend on the redox state of NO produced. Important preliminary data suggest that NO* is the redox form of the endogenous nitrergic neurotransmitter. The aim of this application is to examine the actions of sodium nitroprusside (a NO+ donor), nitrocycteine ( a NO+ donor and putative EDRF), and amine/NO adducts ( NO* donors like DNO). Functional studies will be done to study single channel currents in cell-attached and excised membrane patches. Whole cells and perforated patch currents will be studied to characterize channel currents, the actions of NO donors, and signaling pathways. Molecular expression of the channel proteins in circular muscle will be done with in situ hybridization using cDNA and sequences of published Ca- Cl and Ca small conductance K channels. The effects of NO on single cells will be relate to nitrergic neurotransmission and physiology with microelectrode, mechanical studies and measurement of esophageal motility in vivo.