在不同兰尼碱受体空间排列情况下对心肌细胞钙释放进行建模的随机和确定性方法。

Stochastic and deterministic approaches to modelling calcium release in cardiac myocytes at different spatial arrangements of ryanodine receptors.

作者信息

Iaparov B I, Moskvin A S, Zahradník I, Zahradníková A

机构信息

Research Institute of Physics and Applied Mathematics, Ural Federal University, 620083, Yekaterinburg, Russia.

Department of Theoretical and Mathematical Physics, Ural Federal University, 620083, Yekaterinburg, Russia.

出版信息

Eur Biophys J. 2019 Sep;48(6):579-584. doi: 10.1007/s00249-019-01378-z. Epub 2019 Jun 24.

DOI:10.1007/s00249-019-01378-z

Abstract

Calcium release sites (CRSs) play a key role in excitation-contraction coupling of cardiac myocytes. Recent studies based on electron tomography and super-resolution imaging revealed that CRSs are not completely filled with ryanodine receptors (RyRs) and that the spatial arrangement of RyRs is neither uniform nor static. In this work, we studied the effect of spatial arrangement of RyRs on RyR activation using simulations based on Monte Carlo (MC) and mean-field (MF) approaches. Both approaches showed that activation of RyRs is sensitive to the arrangement of RyRs in the CRS. However, the MF simulations did not reproduce results of MC simulations for non-compact CRSs, suggesting that the approximations used in the MF approach are not suitable for simulation studies of RyRs arrangements observed experimentally. MC simulations revealed the importance of realistic spatial arrangement of RyRs for adequate modelling of calcium release in cardiac myocytes.

摘要

钙释放位点（CRSs）在心肌细胞的兴奋-收缩偶联中起关键作用。最近基于电子断层扫描和超分辨率成像的研究表明，CRSs并未完全充满兰尼碱受体（RyRs），且RyRs的空间排列既不均匀也非静态。在这项工作中，我们使用基于蒙特卡罗（MC）和平均场（MF）方法的模拟研究了RyRs空间排列对RyR激活的影响。两种方法均表明，RyRs的激活对CRSs中RyRs的排列敏感。然而，MF模拟未重现非紧密CRSs的MC模拟结果，这表明MF方法中使用的近似不适用于对实验观察到的RyRs排列进行模拟研究。MC模拟揭示了RyRs实际空间排列对于心肌细胞钙释放的充分建模的重要性。