国家重点基础研究发展规划(973)(2004CB720007), 国家高技术研究发展计划(863)(2007AA02Z457), 国家自然科学基金(30721064, 30730013, 30425035)和美国NIH(R01 TW007269)资助项目.
This work was supported by grants from National Basic Research Program of China(2004CB720007), Hi-Tech Research and Development Program of China(2007AA02Z457). The National Science Foundation of China (30721064, 30730013, 30425035) and National Institutes of Health, USA(R01 TW007269).
钙波作为一种胞内的钙释放通道相互触发而产生的连锁反应广泛存在于多种细胞.在心肌中,由于与心律失常的发生有关,心肌细胞中的钙波近年来引起广泛关注.为了在微观上研究钙波的产生和传播过程,利用激光共聚焦钙成像技术对心肌细胞中的钙波进行了成像.实验和分析发现,钙波的起始是钙火花连续随机募集的过程,因此正常细胞中钙波发生概率很低.钙波传播过程中相邻位点开放的时间间隔接近正态分布,显示传播过程具有较大的随机性.且钙波速度越慢,位点间时间间隔的离散度越高.为了进一步研究这种随机性产生的内在机制,构建了一个数值模型对心肌细胞中的钙波进行模拟.研究证明,钙释放位点开放的随机性能够完整地解释实验中观察到的钙波传播的随机行为.实验分析和数值模拟相互印证,首次明确证明,钙波起始和传播过程的随机性,并揭示了该随机性与钙释放位点开放概率的关系.
The Ca2+ wave is a chain reaction of intracellular Ca2+ release channels through a Ca2+-induced Ca2+ release mechanism. In cardiac myocytes, Ca2+ wave has drawn much attention because it is found to induce arrhythmia genesis. To investigate the microscopic process of wave propagation, Ca2+ imaging was performed with high spatial and temporal resolution via a laser-scanning confocal microscope combined with loose-seal patch clamp. These observation and analysis revealed that Ca2+ waves originated from a stochastic recruiting of Ca2+ release units (CRUs) by a pioneer Ca2+ spark, which had a low possibility in normal cells. During wave propagation, the ‘waiting’ time that the wave propagate between two neighboring CRUs along propagation direction distributed normally, and cells with a lower speed had a more dispersive distribution of ‘waiting’ time. To study the cause of the randomicity, the wave propagation was simulated with a numerical model. The simulation showed that the intrinsic stochastic open process of CRUs can fully explain the above phenomenon. Increasing the maximal open probability of CRUs reduced the randomness of wavefront propagation and enhanced the average velocity of wave meantime. These experimental and numerical results provided an unequivocal quantification for the stochastic behavior of wave initiation and propagation.
唐爱辉,王世强.心肌细胞钙波随机性研究[J].生物化学与生物物理进展,2008,35(8):892-898
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