NEUROMUSCULAR TRANSMISSION IN URINARY SMOOTH MUSCLE

建议建立一个实验室来研究细胞 三者肌间神经肌肉传递的特性 人下尿路主要功能区的细胞内应用 微电极、张力记录和经典药理学 干预。组织将从正常的成人和儿童身上获得 以及接受开放泌尿外科手术的尿肌功能异常。 实验将被设计用来检验机械和电气 肌条对神经刺激的反应及识别 负责复制和取消反应的神经递质 与选定的激动剂和拮抗剂。腺苷的作用 5‘-三磷酸向非肾上腺素能非胆碱能传递 尤其受到关注，因为越来越多的证据支持这一点 化合物在几种肾上腺素能和胆碱能中的这种传递 系统。膜兴奋性的变化，表现为 静息膜电位和对激动剂刺激的反应， 去极化溶液和电刺激将在 正常和异常的尿肌，因为初步证据表明 这种变化可能与病理异常的尿路有关 与临床运动障碍相关的肌肉。希望这一天 这项提议所产生的工作将有助于现有的知识 与排尿相关的正常细胞事件将识别出显著的 尿路功能区的异同 并将有助于了解变化的程度 在细胞机制中对尿路平滑肌的作用 临床尿路运动障碍。 申请人是一名具有三年经验的合格临床泌尿外科医生。 在对平滑肌的实验室研究中。这一奖项将构成一个 为申请人提供发展其研究和临床的主要机会 目标，建立一个独立的实验室来研究基本的 继续临床工作中的尿路平滑肌机制 有神经肌肉膀胱疾病的患者。

A proposal is presented to establish a laboratory to study the cellular properties of neuromuscular transmission in the smooth muscle of the three major functional areas of the human lower urinary tract using intracellular microelectrodes, tension recording, and classical pharmacological intervention. Tissue will be obtained from adults and children with normal and abnormal urinary muscle function undergoing open urologic operations. Experiments will be designed to examine the mechanical and electrical responses of muscle strips to nerve stimulation and to identify the neurotransmitters responsible by reproducing and abolishing the response with selected agonists and antagonists. The contribution of adenosine 5'-triphosphate to non-adrenergic non-cholinergic transmission will be particularly examined because growing evidence supports the role of this compound in such transmission in several adrenergic and cholinergic systems. Changes in membrane excitability as manifested by changes in the resting membrane potential and the response to stimulation by agonists, depolarizing solutions and electrical stimulation will be examined in normal and abnormal urinary muscle because preliminary evidence suggests that such changes may be implicated in pathologically abnormal urinary muscle associated with clinical motility disorders. It is hoped that the work resulting from this proposal will contribute to existing knowledge of normal cellular events associated with voiding, will identify significant similarities and differences among the functional regions of the urinary tract, and will contribute toward understanding the extent to which changes in the cellular mechanisms of urinary tract smooth muscle contribute to clinical disorders of urinary tract motility. The applicant is a qualified clinical urologist with three years experience in the laboratory study of Smooth Muscle. This award would constitute a major opportunity for the applicant to develop his research and clinical goals, to establish an independent laboratory to investigate basic mechanism of urinary tract smooth muscle while continuing his clinical work with patients with neuromuscular bladder disorders.