Evolution of cardiac calcium waves from stochastic calcium sparks
Evolution of cardiac calcium waves from stochastic calcium sparks
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DOI：
10.1016/s0006-3495(01)75998-x
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发表时间：
2001-01-01
影响因子：
3.4
通讯作者：
Balke, CW
中科院分区：
文献类型：
--
作者：
Izu, LT;Wier, WG;Balke, CW
我们提出了一个模型，为研究心肌细胞中的Ca2+ 火花和Ca2+ 波提供了一个统一的框架。该模型的新颖之处在于结合了以下几点：1）通过肌浆网（SR）的Ca2+ 释放单元（CRUs）使用大电流（约20皮安）；2）CRUs的随机Ca2+ 释放（或触发）；3）CRUs在细胞纵向（间隔距离为2微米）和横向（间隔0.4 - 0.8微米）方向上离散、不对称分布；4）Ca2+ 和荧光指示剂的各向异性扩散，以研究从Ca2+ 火花到Ca2+ 波的演变。该模型在自发火花频率、Ca2+ 波速度和波传播模式方面模拟了Ca2+ 火花和Ca2+ 波的重要特征。重要的是，当使用实验测量的CRU Ca2+ 敏感性值（约15微摩尔）时，这些特征得以重现。CRU触发的随机控制很重要，因为它对CRU的Ca2+ 敏感性施加了限制。即使Ca2+ 敏感性适中（约5微摩尔），极高的自发火花频率也会引发大量Ca2+ 波。相比之下，在确定性模型中，当CRU Ca2+ 敏感性足够高时，可能存在一个具有任意大速度的单一Ca2+ 波。低CRU Ca2+ 敏感性（约15微摩尔）、高细胞质Ca2+ 缓冲能力以及CRUs的空间分隔相结合，有助于控制肌浆网Ca2+ 释放的固有不稳定性。这使得在给定足够大的起始区域时Ca2+ 波能够形成和传播，但防止单个火花或一小群火花引发波。
We present a model that provides a unified framework for studying Ca2+ sparks and Ca2+ waves in cardiac cells. The model is novel in combining 1) use of large currents (similar to 20 pA) through the Ca2+ release units (CRUs) of the sarcoplasmic reticulum (SR); 2) stochastic Ca2+ release (or firing) of CRUs; 3) discrete, asymmetric distribution of CRUs along the longitudinal (separation distance of 2 mum) and transverse (separated by 0.4-0.8 mum) directions of the cell; and 4) anisotropic diffusion of Ca2+ and fluorescent indicator to study the evolution of Ca2+ waves from Ca2+ sparks. The model mimics the important features of Ca2+ sparks and Ca2+ waves in terms of the spontaneous spark rate, the Ca2+ wave velocity, and the pattern of wave propagation. Importantly, these features are reproduced when using experimentally measured values for the CRU Ca2+ sensitivity (similar to 15 muM). Stochastic control of CRU firing is important because it imposes constraints on the Ca2+ sensitivity of the CRU. Even with moderate (similar to5 muM) Ca2+ sensitivity the very high spontaneous spark rate triggers numerous Ca2+ waves. In contrast, a single Ca2+ wave with arbitrarily large velocity can exist in a deterministic model when the CRU Ca2+ sensitivity is sufficiently high. The combination of low CRU Ca2+ sensitivity (similar to 15 muM), high cytosolic Ca2+ buffering capacity, and the spatial separation of CRUs help control the inherent instability of SR Ca2+ release. This allows Ca2+ waves to form and propagate given a sufficiently large initiation region, but prevents a single spark or a small group of sparks from triggering a wave.