Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease.
Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease.
复制标题
心脏钙火花的相关超分辨率分析及其在健康和疾病中的分子起源。
作者：
在可兴奋细胞中，钙离子通过ryanodine受体（RyRs）快速释放是细胞质第二信使信号传导的最快类型之一。在心脏中，钙释放的基本事件的快速汇总，即“钙火花”，决定了心肌的收缩。我们采用相关的超分辨率显微镜技术，将大鼠右心室肌细胞的质乳下自发钙火花与局部纳米级RyR2位置联系起来。这揭示了钙火花的积分与局部RyR2s的和之间的陡峭关系。对反复出现的火花位点的分割显示了多个局部RyR2簇的重复和触发的跃变激活的证据。在取自衰竭右心室的肌细胞中，RyR2簇本身表现为消散的形态和碎片化的（较小的）簇。它们在火花特性和钙火花积分与RyR2s局部系综之间的关系上也具有更大的异质性。虽然碎片化（较小）的RyR2簇很少被观察到直接位于较大的火花或反复出现的火花位置，但对通道到通道距离的局部询问证实了每个钙火花的位置与健康和衰竭心室中局部RyR2紧密的非随机簇之间的明确联系。
Rapid release of calcium from internal stores via ryanodine receptors (RyRs) is one of the fastest types of cytoplasmic second messenger signalling in excitable cells. In the heart, rapid summation of the elementary events of calcium release, 'calcium sparks', determine the contraction of the myocardium. We adapted a correlative super-resolution microscopy protocol to correlate sub-plasmalemmal spontaneous calcium sparks in rat right ventricular myocytes with the local nanoscale RyR2 positions. This revealed a steep relationship between the integral of a calcium spark and the sum of the local RyR2s. Segmentation of recurring spark sites showed evidence of repeated and triggered saltatory activation of multiple local RyR2 clusters. In myocytes taken from failing right ventricles, RyR2 clusters themselves showed a dissipated morphology and fragmented (smaller) clusters. They also featured greater heterogeneity in both the spark properties and the relationship between the integral of the calcium spark and the local ensemble of RyR2s. While fragmented (smaller) RyR2 clusters were rarely observed directly underlying the larger sparks or the recurring spark sites, local interrogation of the channel-to-channel distances confirmed a clear link between the positions of each calcium spark and the tight, non-random clustering of the local RyR2 in both healthy and failing ventricles.
登录
查看更多内容
影响因子：
4
作者：
Hou Y;Bai J;Shen X;de Langen O;Li A;Lal S;Dos Remedios CG;Baddeley D;Ruygrok PN;Soeller C;Crossman DJ
通讯作者：
Crossman DJ
影响因子：
4
作者：
Jayasinghe I;Clowsley AH;de Langen O;Sali SS;Crossman DJ;Soeller C
通讯作者：
Soeller C
影响因子：
3.9
作者：
Jayasinghe, Isuru D.;Munro, Michelle;Soeller, Christian
通讯作者：
Soeller, Christian
DOI：
10.1098/rstb.2021.0317
发表时间：
2022-11-21
影响因子：
6.3
作者：
Holmes, M.;Hurley, M. E.;Sheard, T. M. D.;Benson, A. P.;Jayasinghe, I.;Colman, M. A.
通讯作者：
Colman, M. A.
影响因子：
3.4
作者：
Franzini-Armstrong, C;Protasi, F;Ramesh, V
通讯作者：
Ramesh, V