您的位置:网站首页 > 《中文科技期刊数据库》 > 自然科学 > 生物学 > 细胞工程 > 摘要

Role of FK506-binding protein in Ca^2+ spark regulation

《科学通报:英文版》2017年 第19期 | Yan-Ting Zhao Yun-Bo Guo Xue-Xin Fan Hua-Qian Yang Peng Zhou Zheng Chen Qi Yuan Haihong Ye Guang-Ju Ji Shi-Qiang Wang   State Key Laboratory of Membrane Biology College of Life Sciences Peking University Belting 100871 China National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China School of Basic Medical Sciences Beifing Institute for Brain Disorders Center of Schizophrenia Capital Medical University Beijing 100069 China
购物车 | ★ 收藏 | 分享
论文服务:
摘 要:The elementary Ca~(2+) release events, Ca~(2+) sparks, has been found for a quarter of century. However, the molecular regulation of the spark generator, the ryanodine receptor(RyR) on the sarcoplasmic reticulum,remains obscure. Although each subunit of the RyR homotetramer has a site for FK506-binding protein(FKBP), the role of FKBPs in modifying RyR Ca~(2+) sparks has been debated for long. One of the reasons behind the controversy is that most previous studies detect spontaneous sparks, where the mixture with out-of-focus events and local wavelets prevents an accurate characterization of Ca~(2+) sparks. In the present study, we detected Ca~(2+) sparks triggered by single L-type Ca~(2+) channels(LCCs) under loose-seal patch clamp conditions in FK506-treated or FKBP12.6 knockout cardiomyocytes. We found that FKBP dissociation both by FK506 and by rapamycin decreased the Ca~(2+) spark amplitude in ventricular cardiomyocytes. This change was neither due to decreased releasable Ca~(2+) in the sarcoplasmic reticulum,nor explained by changed RyR sensitivity. Actually FK506 increased the LCC-RyR coupling probability and curtailed the latency for an LCC to trigger a RyR Ca~(2+) spark. FKBP12.6 knockout had similar effects as FK506/rapamycin treatment, indicating that the decreased spark amplitude was attributable to the dissociation of FKBP12.6 rather than FKBP12. We also explained how decreased amplitude of spontaneous sparks after FKBP dissociation sometimes appears to be increased or unchanged due to inappropriate data processing. Our results provided firm evidence that without the inter-RyR coordination by functional FKBP12.6, the RyR recruitment during a Ca~(2+) spark would be compromised despite the sensitization of individual RyRs.
【分 类】【生物科学】 > 生物工程学(生物技术) > 细胞工程 > 细胞、组织培养技术 > 细胞培养
【关键词】 FK506 钙火花 结合蛋白 Ca RYANODINE受体 雷帕霉素 RYR 火花发生器
【出 处】 《科学通报:英文版》2017年 第19期 1295-1303页 共9页
【收 录】 中文科技期刊数据库