CHRONIC ETHANOL AND EXCITATION/CONTRACTION COUPLING

长期乙醇与兴奋/收缩耦合

• 批准号: 2855736
• 负责人: MICHELE L SOLEM
• 金额: $ 10.56万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2855736
• 关键词: beta adrenergic agent; biological signal transduction; calcium channel; cardiac myocytes; catecholamines; confocal scanning microscopy; digital imaging; electrophysiology; ethanol; heart contraction; laboratory rat

This proposal is a request for a Mentored Research Scientist Development Award (KO1) that would allow the applicant to establish the following career objectives: (1) develop her expertise in cardiovascular research, which is new to the candidate (2) continue her training in calcium experiments as well as master new skills in electrophysiology (3) develop an independent research program in alcohol research. The Department of Pathology, Anatomy and Cell Biology is committed to in the etiology of alcohol-related diseases, and has been awarded an Alcohol Research Center. The investigators are concerned with the effects of alcohol at the cellular, subcellular and molecular level, and employ a wide range of experimental techniques for these studies. The candidate will be in an ideal environment to develop her scientific career in association with personnel committed to providing mentored support for young scientists in the field of alcohol research. As the focus for establishing her long-term research career in alcohol and heart research, the candidate and preceptor have jointly designed the following research proposal that combines her past technical training with newly established skills and plans for future training in cardiac physiology. Long term alcohol exposure has adverse effects on cardiac tissue. This includes alteration in cardiac contractile functions and reduced responsiveness to catecholamines. In this research plan, an animal model USA alcohol-fed Fischer rats will be employed that has previously been demonstrated to develop alcohol- induced cardiopathologies similar to those found in human alcoholics. Chronic ethanol-induced lesions will be studied at the cellular level using individual ventricular myocytes. Changes in contractility and beta-adrenergic responsiveness due to long-term ethanol exposure will be examined using a high speed digital imaging system and a laser scanning confocal microscope; these systems have been developed in the preceptor's laboratory for similar experiments. Preliminary results from this laboratory demonstrate that chronic ethanol reduces beta- adrenergic enhancement of excitation-contraction coupling and sarcolemmal calcium channel activity. Continuing experiments with single cell imaging, electrophysiology and molecular biology are planned to further characterize the mechanisms responsible for alterations in catecholamine effects on alcohol-impaired myocytes.

该提案是对指导研究科学家发展的请求 奖项（KO1）将允许申请人建立以下内容 职业目标：(1) 发展心血管研究方面的专业知识， 这对候选人来说是新的 (2) 继续她的钙培训 实验并掌握电生理学新技能 (3) 制定酒精研究的独立研究计划。 这 病理学、解剖学和细胞生物学系致力于 酒精相关疾病的病因学，并被授予酒精 研究中心。 调查人员担心的是 在细胞、亚细胞和分子水平上检测酒精，并采用 这些研究的广泛实验技术。 候选人 将在理想的环境中发展她的科学事业 与致力于提供指导支持的人员建立联系 酒精研究领域的年轻科学家。 作为建立她长期酒精研究生涯的重点 和心脏研究，候选人和导师共同设计 以下研究计划结合了她过去的技术 培训新建立的技能和未来培训计划 心脏生理学。 长期接触酒精会对身体产生不良影响 心脏组织。 这包括心脏收缩力的改变 功能并降低对儿茶酚胺的反应。 在这个 研究计划，美国酒精喂养的费舍尔大鼠动物模型将 先前已被证明会产生酒精的雇用 诱发的心脏病与人类酗酒者中发现的类似。 将在细胞水平上研究慢性乙醇引起的病变 使用单个心室肌细胞。 收缩力的变化和 长期接触乙醇导致的β-肾上腺素能反应会 使用高速数字成像系统和激光进行检查 扫描共焦显微镜；这些系统是在 导师实验室进行类似实验。 初步结果 该实验室证明，长期乙醇会降低β- 兴奋-收缩耦合的肾上腺素能增强和 肌膜钙通道活性。 继续实验 计划单细胞成像、电生理学和分子生物学 进一步描述导致变化的机制 儿茶酚胺对酒精损伤的心肌细胞有影响。