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作 者:Yutong Su Yongshen Liang Menghao Xu Beibei Gao Siyuan Zhang Eric Yang Shuai Yin Da Li Zhangqin Huang Wenjun Xie
机构地区:[1]Beijing Engineering Research Center for IoT Software and Systems,Beijing University of Technology,Beijing 100124,China [2]Department of Cardiology,First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China
出 处:《Biophysics Reports》2024年第5期328-335,共8页生物物理学报(英文版)
基 金:supported by grants from the National Natural Science Foundation of China(31971045)。
摘 要:The sarcoplasmic reticulum(SR)primarily serves as the intracellular Ca^(2+)store in cardiac myocytes,mediating cellular function under cardiac physiology and diseases.However,the properties of cardiac SR Ca^(2+)have not yet been fully determined,particularly in rats and mice,which are the most commonly used experimental species in studies on cardiac physiology and diseases.Here,we developed a spatially detailed numerical model to deduce Ca^(2+)movements inside the junctional SR(jSR)cisternae of rat cardiomyocytes.Our model accurately reproduced the jSR Ca^(2+)kinetics of local and global SR Ca^(2+)releases reported in a recent experimental study.With this model,we revealed that jSR Ca^(2+)kinetics was mostly determined by the total release flux via type 2 ryanodine receptor(RyR2)channels but not by RyR2 positioning.Although Ca^(2+)diffusion in global SR was previously reported to be slow,our simulation demonstrated that Ca^(2+)diffused very quickly inside local jSR cisternae and the decrease in the diffusion coefficient resulted in a significant reduction of jSR Ca^(2+)depletion amplitude.Intracellular Ca^(2+)was typically experimentally detected with fluorescence dye.Our simulation revealed that when the dynamical characteristics of fluorescence dye exerted a minimal effect on actual Ca^(2+)mobility inside jSR,the reaction rate of the dye with Ca^(2+)could significantly affect apparent jSR Ca^(2+)kinetics.Therefore,loading a chemical fluorescence dye with fast kinetics,such as Fluo-5N,into SR is important for Ca^(2+)measurement inside SR.Overall,our model provides new insights into deciphering Ca^(2+)handling inside nanoscopic jSR cisternae in rat cardiomyocytes.
关 键 词:Numerical model Sarcoplasmic reticulum CALCIUM Rat cardiomyocytes Fluorescence dye
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