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An adaptation of astronomical image processing enables characterization and functional 3D mapping of individual sites of excitation-contraction coupling in rat cardiac muscle
eLife ( IF 6.4 ) Pub Date : 2017-11-14 , DOI: 10.7554/elife.30425
Qinghai Tian 1 , Lars Kaestner 1 , Laura Schröder 1 , Jia Guo 1 , Peter Lipp 1
Affiliation  

In beating cardiomyocytes, synchronized localized Ca2+ transients from thousands of active excitation-contraction coupling sites (ECC couplons) comprising plasma and sarcoplasmic reticulum membrane calcium channels are important determinants of the heart's performance. Nevertheless, our knowledge about the properties of ECC couplons is limited by the lack of appropriate experimental and analysis strategies. We designed CaCLEAN to untangle the fundamental characteristics of ECC couplons by combining the astronomer's CLEAN algorithm with known properties of calcium diffusion. CaCLEAN empowers the investigation of fundamental properties of ECC couplons in beating cardiomyocytes without pharmacological interventions. Upon examining individual ECC couplons at the nanoscopic level, we reveal their roles in the negative amplitude-frequency relationship and in β-adrenergic stimulation, including decreasing and increasing firing reliability, respectively. CaCLEAN combined with 3D confocal imaging of beating cardiomyocytes provides a functional 3D map of active ECC couplons (on average, 17,000 per myocyte). CaCLEAN will further enlighten the ECC-couplon-remodelling processes that underlie cardiac diseases.

中文翻译:

天文图像处理的适应使得能够对大鼠心肌中激发-收缩耦合的各个位点进行表征和功能 3D 映射

在跳动的心肌细胞中,来自包括血浆和肌浆网膜钙通道在内的数千个活跃的兴奋-收缩耦合位点(ECC 耦合器)的同步局部 Ca2+ 瞬变是心脏性能的重要决定因素。然而,由于缺乏适当的实验和分析策略,我们对 ECC 耦合器特性的了解有限。我们设计了 CaCLEAN,通过将天文学家的 CLEAN 算法与已知的钙扩散特性相结合,来解开 ECC 耦合器的基本特征。CaCLEAN 可以在没有药物干预的情况下研究 ECC 偶联物在跳动心肌细胞中的基本特性。在纳米级检查单个 ECC 耦合剂后,我们揭示了它们在负幅频关系和 β-肾上腺素能刺激中的作用,包括分别降低和增加发射可靠性。CaCLEAN 与跳动心肌细胞的 3D 共聚焦成像相结合,提供了活动 ECC 耦合器的功能性 3D 图(平均每个心肌细胞 17,000 个)。CaCLEAN 将进一步启发作为心脏疾病基础的 ECC 耦合重塑过程。
更新日期:2017-11-14
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