Intra/Intercellular/physiology/mitochodria/whole hearts

细胞内/细胞间/生理学/线粒体/整个心脏

• 批准号: 7107245
• 负责人: MARTIN K SLODZINSKI
• 金额: $ 13.31万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107245
• 关键词: adenosine triphosphate; calcium flux; cardiovascular imaging /visualization; cell biology; cell component structure /function; confocal scanning microscopy; cytoprotection; free radical oxygen; guinea pigs; heart; intracellular; membrane potentials; mitochondria; myocardial ischemia /hypoxia; potassium channel; reperfusion; technology /technique development

DESCRIPTION (provided by applicant):This grant application proposes a 5-year training program to launch an academic career of an independent cardiovascular physiologist and a clinical anesthesiologist. In July 2002, the principal investigator completed residency training in the Department of Anesthesiology and Critical Care Medicine at the Johns Hopkins University and a research fellowship in the Department of Medicine, Division of Cardiology, The Institute of Molecular Cardiobiology, supervised by Brian O'Rourke, Ph.D., and Eduardo Marban, M.D., Ph.D. This unique interdepartmental training with abundant intellectual and physical resources honed the applicant's creative, scientific and clinical skills. This proposal integrates mitochondrial physiology with a clinically significant problem (ischemia-reperfusion injury) using a novel platform technology (multi-photon imaging of an intact heart). Drs. O'Rourke and Marban will mentor the principal investigator. Dr. Marban is Director of the Institute of Cardiobiology, with a well-established record of training successful cardiac physiologists. Dr. O'Rourke is Director of The Johns Hopkins University Imaging Facility and a leader in cardiac mitochondrial physiology. In addition, an advisory committee of highly successful, senior anesthesiologists, physician-scientists will provide scientific and career guidance. The project will focus on intracellular and intercellular physiology of mitochondrial during ischemia and reperfusion. Recent work in the O'Rourke lab demonstrated mitochondrial membrane potential oscillations in isolated cardiomyocytes and the key role of mitochondrial KATP channels in cardio- protection. The proposed experiments will examine mitochondrial physiology in the intact heart. The specific aims are: 1) Developing multi-photon confocal microscopy as a platform technology to examine intracellular and intercellular events in the intact heart, 2) Evaluating possible mechanisms of mitochondrial ATP-sensitive potassium channels in cardioprotection in an intact heart, 3) Describe mitochondrial membrane potential oscillations in the intact heart and relate these findings to reactive oxygen species generation. This novel project will examine sub-cellular, cellular, and multi-cellular mitochondrial physiological phenomena in an intact heart.

描述（由申请人提供）：该拨款申请提出了一个为期 5 年的培训计划，以启动独立心血管生理学家和临床麻醉师的学术生涯。 2002年7月，首席研究员在约翰·霍普金斯大学麻醉学和重症监护医学系完成了住院医师培训，并在分子心脏病学研究所心脏病学部医学系完成了研究奖学金，由布莱恩·奥罗克（Brian O'Rourke）指导，博士，和爱德华多·马尔班，医学博士，博士。 这种独特的跨部门培训，丰富的智力和体力资源，磨练了申请人的创造性、科学性和临床技能。该提案使用新颖的平台技术（完整心脏的多光子成像）将线粒体生理学与临床显着问题（缺血再灌注损伤）结合起来。 博士。奥罗克和马班将指导首席研究员。 Marban 博士是心脏生物学研究所所长，在培养成功的心脏生理学家方面拥有良好的记录。 O'Rourke 博士是约翰·霍普金斯大学成像设施的主任，也是心脏线粒体生理学领域的领导者。 此外，由非常成功的高级麻醉师组成的咨询委员会， 医生科学家将提供科学和职业指导。 该项目将重点研究缺血和再灌注期间线粒体的细胞内和细胞间生理学。 O'Rourke 实验室最近的工作证明了离体心肌细胞中的线粒体膜电位振荡以及线粒体 KATP 通道在心肌细胞中的关键作用。 保护。 拟议的实验将检查完整心脏中的线粒体生理学。 具体目标是：1) 开发多光子共聚焦显微镜作为检查完整心脏中细胞内和细胞间事件的平台技术，2) 评估线粒体 ATP 敏感钾通道在完整心脏心脏保护中的可能机制，3) 描述完整心脏中线粒体膜电位的振荡，并将这些发现与活性氧的产生联系起来。 这个新项目将检查完整心脏中的亚细胞、细胞和多细胞线粒体生理现象。