E-C coupling efficiency in hibernation and heart failure

冬眠和心力衰竭中的电-电耦合效率

• 批准号: 7433209
• 负责人: SHI-QIANG WANG
• 金额: $ 5.12万
• 依托单位: PEKING UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-27 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7433209
• 关键词: Address; Attenuated; Cardiac; Cardiovascular Diseases; Chinese People; Closure; Coupling; Data; Doctor of Philosophy; Down-Regulation; Failure; Future; Goals; Heart; Heart failure; Hibernation; Hypertrophy; Image; Imaging Techniques; In Situ; Kinetics; Lead; Mammals; Measures; Methodology; Modeling; Modification; Molecular; Molecular Target; Muscle Cells; Nature; Numbers; Property; Publishing; Rattus; Regulation; Reporting; Research; Research Design; Research Personnel; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Signal Transduction; Spermophilus; Techniques; Testing; attenuation; awake; base; experience; heart cell; improved; programs; quantum

DESCRIPTION (provided by applicant): While the efficiency of cardiac excitation-contraction (E-C) coupling in heart failure undergoes a defective down-regulation, that in hibernating mammals is up-regulated. The long-term objective of the proposed research is to find the cellular and molecular mechanism of E-C coupling regulation in hibernators, and seek to apply them in rescuing failing hearts. The specific aims, hypotheses and research designs are: 1) to test the hypothesis that the Ca2+ influx tends to activate more Ca2+ release from sarcoplasmic reticulum hibernating than awake hibernators such that the E-C coupling efficiency can be increased. This will be achieved by combining electrophysiological recording and confocal Ca2+ imaging. 2) to test the hypothesis that, in a single E-C coupling unit, Ca2+ release channels become more responsive to single-channel Ca2+ trigger during hibernation, but less in impaired E-C coupling during heart failure. The intermolecular coupling fidelity and latency and signal mass of Ca2+ sparks in failing and hibernating models will be analyzed using our recently developed loose-patch confocal imaging. 3) to test the hypothesis that different changes in the unitary properties of Ca2+ underlie the opposite alternation of E-C coupling efficiency in hibernation and heart failure. The strength and kinetics of single-channel Ca2+ release and micro-recruitment of release channels in failure and hibernation models will be assessed by analyzing the quantal property of Ca2+ sparks recently found by this PI. The above study will reveal the molecular details underlying the opposite modifications of E-C coupling occurred in hibernation and heart failure. This will provide necessary and important basis for further studies to rescue failing heart with strategies employed by hibernators.

描述（由申请人提供）：虽然心力衰竭中心脏兴奋-收缩（E-C）耦合的效率经历了有缺陷的下调，但冬眠哺乳动物中的心脏兴奋-收缩（E-C）耦合效率却上调。该研究的长期目标是找到冬眠者E-C耦合调节的细胞和分子机制，并寻求将其应用于挽救衰竭的心脏。具体目标、假设和研究设计是：1）检验以下假设：Ca2+流入往往会激活冬眠者肌浆网比清醒冬眠者释放更多Ca2+，从而提高E-C耦合效率。这将通过结合电生理记录和共焦 Ca2+ 成像来实现。 2) 检验以下假设：在单个 E-C 耦合单元中，Ca2+ 释放通道在冬眠期间对单通道 Ca2+ 触发的反应更加敏感，但在心力衰竭期间受损的 E-C 耦合中反应较少。将使用我们最近开发的松散斑块共聚焦成像来分析失败和冬眠模型中 Ca2+ 火花的分子间耦合保真度、延迟和信号质量。 3) 检验以下假设：Ca2+ 单一性质的不同变化是冬眠和心力衰竭中 E-C 耦合效率相反交替的基础。通过分析该 PI 最近发现的 Ca2+ 火花的量子特性，将评估故障和冬眠模型中单通道 Ca2+ 释放以及释放通道微招募的强度和动力学。上述研究将揭示冬眠和心力衰竭中发生的 E-C 耦合相反修饰背后的分子细节。这将为进一步研究利用冬眠者采用的策略来挽救衰竭的心脏提供必要且重要的基础。