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: 7612131
• 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/7612131
• 关键词: Address; Attenuated; Cardiac; Cardiovascular Diseases; Chinese People; 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; Property; Publishing; Rattus; Regulation; Reporting; Research; Research Design; Research Personnel; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; 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.

说明（由申请人提供）：虽然心力衰竭中心脏兴奋-收缩（E-C）偶联的效率经历缺陷性下调，但冬眠哺乳动物中的效率上调。本研究的长期目标是探索冬眠动物E-C偶联调控的细胞和分子机制，并将其应用于衰竭心脏的抢救。具体目的、假设和研究设计为：1）验证Ca ~（2+）内流激活冬眠肌浆网释放Ca ~（2+）的可能性，从而提高E-C偶联效率。这将通过结合电生理记录和共聚焦Ca 2+成像来实现。2)以验证以下假设：在单个E-C耦合单元中，Ca 2+释放通道在冬眠期间对单通道Ca 2+触发变得更敏感，但在心力衰竭期间受损的E-C耦合中反应较低。分子间耦合保真度和延迟和信号质量的钙离子火花失败和冬眠模型将使用我们最近开发的松散补丁共聚焦成像分析。3)以验证冬眠和心力衰竭时E-C偶联效率的相反变化是由于Ca ~（2+）的整体性质发生了不同变化的假设。通过分析本PI最近发现的Ca 2+火花的量子特性，评估衰竭和冬眠模型中单通道Ca 2+释放和释放通道微募集的强度和动力学。上述研究将揭示冬眠和心力衰竭时E-C偶联发生相反改变的分子细节。这将为进一步研究冬眠动物的策略对衰竭心脏的抢救提供必要的重要依据。

项目成果

Ca2+ cycling in heart cells from ground squirrels: adaptive strategies for intracellular Ca2+ homeostasis.

• DOI: 10.1371/journal.pone.0024787
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Li XC;Wei L;Zhang GQ;Bai ZL;Hu YY;Zhou P;Bai SH;Chai Z;Lakatta EG;Hao XM;Wang SQ
• 通讯作者: Wang SQ

Dark rearing alters the short-term synaptic plasticity in visual cortex.

黑暗饲养会改变视觉皮层的短期突触可塑性。

• DOI: 10.1016/j.neulet.2007.05.053
• 发表时间: 2007
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Tang,Ai-Hui;Chai,Zhen;Wang,Shi-Qiang
• 通讯作者: Wang,Shi-Qiang

In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.

体内抑制 MicroRNA-24 可防止主动脉缩窄小鼠向失代偿性肥大转变

• DOI: 10.1161/circresaha.112.300806
• 发表时间: 2013-02-15
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: Li RC;Tao J;Guo YB;Wu HD;Liu RF;Bai Y;Lv ZZ;Luo GZ;Li LL;Wang M;Yang HQ;Gao W;Han QD;Zhang YY;Wang XJ;Xu M;Wang SQ
• 通讯作者: Wang SQ

Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells.

• DOI: 10.1093/cvr/cvs195
• 发表时间: 2012-09
• 期刊: Cardiovascular research
• 影响因子: 10.8
• 作者: Hao Wu;Ming Xu;Rong Li;Liang Guo;Ying-Si Lai;Shi-Ming Xu;Sufang Li;Quan-Long Lü;Lin-Lin Li-Lin;Haibo Zhang;You-yi Zhang;Chuan-Mao Zhang;Shi-Qiang Wang

Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in hypertrophy.

• DOI: 10.1371/journal.pbio.0050021
• 发表时间: 2007-02
• 期刊: PLOS BIOLOGY
• 影响因子: 9.8
• 作者: Xu, Ming;Zhou, Peng;Xu, Shi-Ming;Liu, Yin;Feng, Xinheng;Bai, Shu-Hua;Bai, Yan;Hao, Xue-Mei;Han, Qide;Zhang, Youyi;Wang, Shi-Qiang
• 通讯作者: Wang, Shi-Qiang