KINETICS OF COLONIC SMOOTH MUSCLE RELAXATION

结肠平滑肌松弛的动力学

• 批准号: 3086571
• 负责人: ROBERT F WILLENBUCHER
• 金额: $ 9.65万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3086571
• 关键词: actins; calcium flux; colon; cyclic AMP; dyes; laboratory rabbit; muscle contraction; muscle relaxation; myosins; smooth muscle; training

This proposal describes a course of training and research designed to establish the candidate as an independent biomedical investigator. The candidate has chosen sponsors who are well suited as mentors and are experts in their field. Dr. Julio Vergara is an expert in calcium control mechanisms and imaging techniques and Dr. William J. Snape, Jr. is an expert in smooth muscle physiology and pathophysiology. The candidate seeks to answer the question: Does cAMP relax colonic smooth muscle through a primary effect on cytosolic calcium or directly on actin myosin cross- bridge formation? To accomplish this goal, two phases of research and training are proposed. During Phase I, the candidate will pursue formal course work in cell and muscle physiology as well as participating in the academically enriched environment of the UCLA Department of Physiology. The candidate will develop a kinetic model relating calcium and isometric force transients in rabbit colonic circular muscle strips. During Phase II, the proposed kinetic model will be used to quantitatively assess the role of cAMP on smooth muscle contraction and relaxation. The specific experimental aims are: 1) to measure intracellular calcium and isometric stress simultaneously, 2) to validate this method with two calcium sensitive dyes (fluo-3 and indo-1), 3) to measure the kinetic parameters of these calcium and force transients, 4) to assess the effect of photolytically released cAMP (caged cAMP) on the measured kinetic relationships, and 5) to correlate cAMP-mediated regulation of the contractile apparatus to biochemical studies of myosin light chain kinase. It is though that a better understanding of the mechanisms that control smooth muscle contraction and relaxation may lead to important, new treatments in patients with disorders of colonic transit and motility such as idiopathic constipation and the irritable bowel syndrome.

本建议介绍了一个培训和研究课程， 确定候选人为独立的生物医学研究员。 的 候选人选择了非常适合作为导师的赞助商， 他们领域的专家。 Julio Vergara博士是钙控制方面的专家 以及小威廉·J·斯内普博士。是一 平滑肌生理学和病理生理学专家。 候选 试图回答这个问题：cAMP是否通过 对细胞质钙或直接对肌动蛋白肌球蛋白交叉的主要影响， 桥形？ 为了实现这一目标，两个阶段的研究和 提出了培训。 在第一阶段，候选人将寻求正式的 在细胞和肌肉生理学的课程工作，以及参与 加州大学洛杉矶分校生理学系的学术丰富的环境。 候选人将开发一个与钙和等长收缩相关的动力学模型 兔结肠环形肌条的力瞬变。 在阶段 II，所提出的动力学模型将用于定量评估 cAMP对平滑肌收缩和舒张的作用。 具体 本实验的目的是：1）测定细胞内钙离子浓度， 同时施加应力，2）用两种钙离子验证该方法 敏感染料（fluo-3和indo-1），3）测量动力学参数 这些钙和力瞬变，4）以评估 光解释放的cAMP（笼化cAMP）对测量的动力学的影响 关系，和5）关联cAMP介导的调节， 肌球蛋白轻链激酶的生化研究。 尽管更好地理解控制 平滑肌收缩和舒张可能导致重要的，新的 结肠运输和动力障碍患者的治疗， 如特发性便秘和肠易激综合征。