Spatiotemporal characteristics of SR Ca2+ uptake and release in detubulated rat ventricular myocytes
Spatiotemporal characteristics of SR Ca2+ uptake and release in detubulated rat ventricular myocytes
复制标题
DOI：
10.1016/j.yjmcc.2005.08.005
复制
发表时间：
2005-11-01
影响因子：
5
通讯作者：
Orchard, CH
中科院分区：
文献类型：
--
作者：
Brette, F;Despa, S;Orchard, CH
在心室肌细胞中，肌浆网（SR）Ca 2+负荷是SR Ca 2+释放的关键决定因素。这种释放通常主要发生在肌膜内陷（t-小管）的SR连接处，确保整个细胞同步SR Ca 2+释放。但在Ca ~（2+）超负荷条件下，可发生自发性SR Ca ~（2+）释放和传播Ca ~（2+）波，这是有利的。我们使用去微管的大鼠心室肌细胞，以确定依赖于SR Ca 2+负荷的Ca 2+波传播，和SR Ca 2+摄取和自发释放的作用的t-小管。SR Ca 2+耗竭后，去微管心肌细胞中Ca 2+瞬时振幅（和SR Ca 2+负荷）的恢复比对照心肌细胞慢（半最大恢复：9.9 +/- 1.4 vs. 5.5 +/- 0.7次搏动）。在去微管的心肌细胞的范围和速度的Ca 2+从细胞周边的传播增加，每拍和急剧依赖于SR Ca 2+负荷。异丙肾上腺素（ISO）加速恢复，增加最大传播速度，降低阈值SR的Ca 2+负荷的传播。Ca 2+火花频率在整个控制细胞宽度上是均匀的，并且在去微管细胞的外围是相似的。然而，在去微管细胞的内部钙火花频率低75%（尽管可比的本地SR钙负荷），这种横向火花频率的配置文件是类似的心房肌细胞。我们的结论是：（1）t-小管Ca ~（2+）通量通常控制SR Ca ~（2+）再填充;（2）Ca ~（2+）波的传播急剧依赖于SR Ca ~（2+）含量;（3）SR-t-小管连接在启动SR Ca ~（2+）释放中是重要的;（4）ISO增强SR Ca ~（2+）释放的传播，但不启动SR Ca ~（2+）释放事件（对于给定的SR Ca ~（2+）负荷）。(c)2005爱思唯尔有限公司保留所有权利。
In cardiac ventricular myocytes, sarcoplasmic reticulum (SR) Ca2+ load is a key determinant of SR Ca2+ release. This release normally occurs predominantly from SR junctions at sarcolemmal invaginations (t-tubules), ensuring synchronous SR Ca2+ release throughout the cell. However under conditions of Ca2+ overload, spontaneous SR Ca2+ release and propagating Ca2+ waves can occur, which are pro-arrhythmic. We used detubulated rat ventricular myocytes to determine the dependence of Ca2+ wave propagation on SR Ca2+ load, and the role of t-tubules in SR Ca2+ uptake and spontaneous release. After SR Ca2+ depletion, recovery of Ca2+ transient amplitude (and SR Ca2+ load) was slower in detubulated than control myocytes (half-maximal recovery: 9.9 +/- 1.4 vs. 5.5 +/- 0.7 beats). In detubulated myocytes the extent and velocity of Ca2+ propagation from the cell periphery increased with each beat and depended steeply on SR Ca2+ load. Isoproterenol (ISO) accelerated recovery, increased maximal propagation velocity and reduced the threshold SR Ca2+ load for propagation. Ca2+ spark frequency was uniform across control cell width and was similar at the periphery of detubulated cells. However, internal Ca2+ spark frequency in detubulated cells was 75% lower (despite comparable local SR Ca2+ load); this transverse spark frequency profile was similar to that in atrial myocytes. We conclude that: (1) t-tubule Ca2+ fluxes normally control SR Ca2+ refilling; (2) Ca2+ wave propagation depends steeply on SR Ca2+ content (3) SR-t-tubule junctions are important in initiating SR Ca2+ release and (4) ISO enhances propagation of SR Ca release, but not the initiation of SR Ca release events (for given SR Ca2+ loads). (c) 2005 Elsevier Ltd. All rights reserved.