PHYSIOLOGY AND PATHOPHYSIOLOGY OF ESOPHAGEAL MOTILITY

描述：这些研究的总体目标是了解 平滑肌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， 食管平滑肌离子通道， 活性是由NO介导的尚未确定。 初步数据 表明NO改变了钙刺激的氯化物的活性 电流（最近由PI确定）产生其生理 对食管肌细胞的影响。 NO也可能改变一种新的钙离子- PI在髂肌细胞中描述的激活的K通道。 的 PI还证明了NO供体的作用依赖于氧化还原 NO的产生。重要的初步数据表明，NO* 是 内源性氮能神经递质的氧化还原形式。 的目的 应用是检查硝普钠（一个NO+）的行动 供体）、硝基半胱氨酸（NO+供体和推定的EDRF）和胺/NO 加合物（NO* 供体如DNO）。将进行功能研究， 单通道电流在细胞附着和切除的膜补丁。 将研究全细胞和穿孔斑电流， 通道电流、NO供体的作用和信号传导途径。 环形肌中通道蛋白的分子表达将是 使用cDNA和已发表的Ca- Cl和Ca小电导K通道。NO对单个细胞的作用 将涉及氮能神经传递和生理学， 微电极、力学研究和食管运动测量 in vivo.

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.