The effects of the immunophilins, FKBP12 and FKBP12.6, and phosphorylation on type II ryanodine receptor (RyR2) arrangement and function were examined using correlation microscopy (line scan confocal imaging of Ca²⁺ sparks and dual-tilt electron tomography) and dSTORM imaging of permeabilized Wistar rat ventricular myocytes. Saturating concentrations (10 µmol/L) of either FKBP12 or 12.6 significantly reduced the frequency, spread, amplitude and Ca²⁺ spark mass relative to control, while the tomograms revealed both proteins shifted the tetramers into a largely side-by-side configuration. Phosphorylation of immunophilin-saturated RyR2 resulted in structural and functional changes largely comparable to phosphorylation alone. dSTORM images of myocyte surfaces demonstrated that both FKBP12 and 12.6 significantly reduced RyR2 cluster sizes, while phosphorylation, even of immunophilin-saturated RyR2, increased them. We conclude that both RyR2 cluster size and the arrangement of tetramers within clusters is dynamic and respond to changes in the cellular environment. Further, these changes affect Ca²⁺ spark formation.

中文翻译：

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心脏ryanodine受体分布是动态的，并通过辅助蛋白和翻译后修饰而改变

使用相关显微镜（Ca ²⁺火花的线扫描共聚焦成像和双倾斜电子断层成像）和dSTORM成像检查了亲免蛋白，FKBP12和FKBP12.6以及磷酸化对II型ryanodine受体（RyR2）排列和功能的影响。透化的Wistar大鼠心室肌细胞。FKBP12或12.6的饱和浓度（10 µmol / L）显着降低了频率，扩散，幅度和Ca ²⁺相对于对照而言，火花质量较高，而断层图显示两种蛋白质均使四聚体转变为很大程度上并排的构型。亲免蛋白饱和的RyR2的磷酸化导致结构和功能的变化，与单独的磷酸化相当。肌细胞表面的dSTORM图像显示FKBP12和12.6均显着减小了RyR2簇的大小，而磷酸化（甚至是亲免疫蛋白饱和的RyR2）使它们增加了。我们得出的结论是，RyR2簇的大小和簇内四聚体的排列都是动态的，并能响应细胞环境的变化。此外，这些变化影响Ca ²⁺火花的形成。