REGULATION OF WORK CAPACITY IN CARDIAC MYOCYTES

心肌细胞工作能力的调节

• 批准号: 2771566
• 负责人: Kerry S McDonald
• 金额: $ 13.67万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2771566
• 关键词: biomechanics; calcium ion; heart cell; laboratory rat; muscle cells; muscle function; myocardium; myosins; sarcomeres; tissue /cell culture

DESCRIPTION (adapted from the applicant's abstract): The determinants of work capacity (i.e., power output) will be examined by measuring power-load curves in single permeabilized rat cardiac myocytes. The role of myosin heavy chain (MHC) will be assessed by examining power-load curves in myocytes with varying mixtures of alpha (a) and beta (b) myosin heavy chain. The applicant expects that these studies on the mixtures will provide insight on the role of force generating or detachment in determining the power output. The contribution (direct effect on the cross-bridge transitions or an indirect effect of thin filament activation) of Ca2+ to power output will be evaluated using varying concentrations of calcium in the experiments or changing the sensitivity of the thin filament system to calcium by extracting TnC or using calcium sensitizing agents. The role of titin on shortening dependence of power output will be assessed by studying myocytes with and without titin, while the effect of the extracellular matrix will be evaluated by using multicellular preparations and comparing them with the single myocyte data. The effect of sarcomere length and interfillament spacing on power output will also be evaluated. The alterations in sarcomere length will also be used to ascertain if attachment rates and detachment rates are the determinants of the power output. Finally, some experiments will be carried out on rat skeletal fibers for the purpose of comparison and validation.

描述(改编自申请人的摘要)：决定因素 工作能力(即功率输出)将通过测量功率负载来检查 单个通透性大鼠心肌细胞的曲线。肌球蛋白的作用 重链(MHC)将通过检查中的功率-负载曲线进行评估 肌球蛋白重链含有不同的α(A)和β(B)混合物的肌细胞。 申请人期望这些关于混合物的研究将提供 洞察力量产生或分离在决定 功率输出。贡献(对跨桥的直接影响 钙离子的转变或细丝激活的间接效应) 功率输出将使用不同浓度的钙进行评估 改变细丝系统对温度的敏感性的实验 通过提取TNC或使用钙增敏剂来获得钙。的作用 将通过研究评估TITIN对缩短功率输出的依赖 肌细胞有无肌动蛋白，而细胞外的影响 将通过使用多细胞制剂和比较来评估基质 他们与单个心肌细胞的数据。肌节长度和肌节长度的影响 还将评估功率输出中的填充物间距。这个 肌节长度的改变也将被用来确定是否附着 速率和分离率是功率输出的决定因素。 最后，将在大鼠骨骼纤维上进行一些实验 比较和验证的目的。