兰尼碱受体弥散破坏衰竭心肌细胞的钙释放。
Ryanodine receptor dispersion disrupts Ca release in failing cardiac myocytes.
机构信息
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
KG Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway.
出版信息
Elife. 2018 Oct 30;7:e39427. doi: 10.7554/eLife.39427.
Reduced cardiac contractility during heart failure (HF) is linked to impaired Ca release from Ryanodine Receptors (RyRs). We investigated whether this deficit can be traced to nanoscale RyR reorganization. Using super-resolution imaging, we observed dispersion of RyR clusters in cardiomyocytes from post-infarction HF rats, resulting in more numerous, smaller clusters. Functional groupings of RyR clusters which produce Ca sparks (Ca release units, CRUs) also became less solid. An increased fraction of small CRUs in HF was linked to augmented 'silent' Ca leak, not visible as sparks. Larger multi-cluster CRUs common in HF also exhibited low fidelity spark generation. When successfully triggered, sparks in failing cells displayed slow kinetics as Ca spread across dispersed CRUs. During the action potential, these slow sparks protracted and desynchronized the overall Ca transient. Thus, nanoscale RyR reorganization during HF augments Ca leak and slows Ca release kinetics, leading to weakened contraction in this disease.
心力衰竭（HF）期间心脏收缩力降低与兰尼碱受体（RyRs）从钙离子释放受损有关。我们研究了这种缺陷是否可以追溯到纳秒级 RyR 重组。使用超分辨率成像，我们观察到梗死后 HF 大鼠心肌细胞中 RyR 簇的分散，导致更多数量的较小簇。产生钙火花（钙释放单位，CRU）的 RyR 簇的功能分组也变得不那么紧密。HF 中较小的 CRU 比例增加与增加的“沉默”钙泄漏有关，而不是以火花的形式可见。HF 中常见的较大多簇 CRU 也表现出低保真火花生成。当成功触发时，衰竭细胞中的火花显示出缓慢的动力学，因为 Ca 扩散到分散的 CRU 上。在动作电位期间，这些缓慢的火花延长并使整体 Ca 瞬变失步。因此，HF 期间纳秒级 RyR 重组会增加钙泄漏并减慢钙释放动力学，导致疾病中收缩力减弱。
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