SPATIAL NONUNIFORMITIES IN [CA2+](I) DURING EXCITATION-CONTRACTION COUPLING IN CARDIAC MYOCYTES
SPATIAL NONUNIFORMITIES IN [CA2+](I) DURING EXCITATION-CONTRACTION COUPLING IN CARDIAC MYOCYTES
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DOI：
10.1016/s0006-3495(94)80677-0
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发表时间：
1994-11-01
影响因子：
3.4
通讯作者：
LEDERER, WJ
中科院分区：
文献类型：
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作者：
CANNELL, MB;CHENG, H;LEDERER, WJ
用荧光钙指示剂Fluo-3和激光扫描共聚焦显微镜观察了成年大鼠心肌细胞内钙（[Ca ~（2+）]（i））瞬变。我们发现电诱发的[Ca 2 +]（i）瞬变在[Ca 2 +]（i）瞬变期间在细胞内的所有点并不以均匀的速率上升。在去极化后立即观察到[Ca 2 +]（i）的这些空间不均匀性，并且在[Ca 2 +]（i）瞬变峰出现时基本上消失。重要的是，[Ca 2 +]（i）中的一些空间非均匀性在搏动之间的位置随机变化。空间特征的非均匀性的分析表明，它们产生的随机性SR钙释放通道的激活。低浓度Cd 2+显著增强[Ca 2 +]（i）的不均匀性，表明L型钙通道的激活是钙瞬变的激活剂钙的主要来源。此外，在这些条件下的钙释放的模式是非常相似的自发钙火花，在静息条件下观察到的，这是由于自发的钙从SR释放。在正常条件下诱发的[Ca 2 +]（i）瞬态的空间不均匀性可以解释的时间和空间的总和的大量的钙火花，其激活是一个随机过程。结果进行了讨论相对于一个随机的局部控制模型的兴奋-收缩（E-C）耦合，它提出了E-C耦合的基本单元由一个二氢吡啶受体激活一个小组的ryanodine受体（可能是四个）在一个正方形包装模型。
The intracellular calcium ([Ca2+](i)) transient in adult rat heart cells was examined using the fluorescent calcium indicator fluo-3 and a laser scanning confocal microscope. We find that the electrically evoked [Ca2+](i) transient does not rise at a uniform rate at all points within the cell during the [Ca2+](i) transient. These spatial non-uniformities in [Ca2+](i) are observed immediately upon depolarization and largely disappear by the time the peak of the [Ca2+](i) transient occurs. Importantly, some of the spatial non-uniformity in [Ca2+](i) varies randomly in location from beat to beat. Analysis of the spatial character of the non-uniformities suggests that they arise from the stochastic nature of the activation of SR calcium-release channels. The non-uniformities in [Ca2+](i) are markedly enhanced by low concentrations of Cd2+, suggesting that activation of L-type calcium channels is the primary source of activator calcium for the calcium transient. In addition, the pattern of calcium release in these conditions was very similar to the spontaneous calcium sparks that are observed under resting conditions and which are due to spontaneous calcium release from the SR. The spatial non-uniformity in the evoked [Ca2+](i) transient under normal conditions can be explained by the temporal and spatial summation of a large number of calcium sparks whose activation is a stochastic process. The results are discussed with respect to a stochastic local control model for excitation-contraction (E-C) coupling, and it is proposed that the fundamental unit of E-C coupling consists of one dihydropyridine receptor activating a small group of ryanodine receptors (possibly four) in a square packing model.