Large currents generate cardiac Ca2+ sparks
Large currents generate cardiac Ca2+ sparks
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DOI：
10.1016/s0006-3495(01)75997-8
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发表时间：
2001-01-01
影响因子：
3.4
通讯作者：
Wier, WG
中科院分区：
文献类型：
--
作者：
Izu, LT;Mauban, JRH;Wier, WG
先前的心肌钙离子（Ca²⁺）火花模型假定，通过Ca²⁺释放单元（CRUs）的Ca²⁺电流约为1 - 2皮安（pA），产生的火花其荧光强度峰值比率约为2.0，半高全宽（FWHM）约为1微米。在此，我们呈现实际的Ca²⁺火花，其F/F₀峰值大于6，半高全宽约为2微米，以及此类火花的一个数学模型，其主要特征是潜在的Ca²⁺电流大得多。假定反应速率无限且无内源性缓冲物质，我们得出产生半高全宽为2微米的Ca²⁺火花所需的下限约为11皮安。在实际条件下，CRU电流必须约为20皮安才能产生半高全宽为2微米的Ca²⁺火花。对于大于或等于5皮安的电流，计算得出的火花幅度（F/F₀）较大（根据缓冲模型约为6 - 12）。我们考虑了几种可能在不使用大电流的情况下产生半高全宽约为2微米的火花的因素。可能的蛋白质 - 染料相互作用使半高全宽略有增加。假设的Ca²⁺“夸克”几乎没有影响，共聚焦显微镜对火花的模糊作用也是如此。一组CRUs，每个同时产生10皮安的电流，可以产生半高全宽约为2微米的火花。我们得出结论：心肌Ca²⁺火花的峰值幅度比先前认为的要大得多，如此大的Ca²⁺火花与测量得到的约2微米的半高全宽是相符的，并且潜在的Ca²⁺电流在10 - 20皮安的范围内。
Previous models of cardiac Ca2+ sparks have assumed that Ca2+ currents through the Ca2+ release units (CRUs) were similar to1-2 pA, producing sparks with peak fluorescence ratio of similar to2.0 and a full-width at half maximum (FWHM) of similar to1 mum Here, we present actual Ca2+ sparks with peak F/F-o of >6 and a FWHM of similar to2 mum, and a mathematical model of such sparks, the main feature of which is a much larger underlying Ca2+ current. Assuming infinite reaction rates and no endogenous buffers, we obtain a lower bound of similar to 11 pA needed to generate a Ca2+ spark with FWHM of 2 mum. Under realistic conditions, the CRU current must be similar to 20 pA to generate a 2-mum Ca2+ spark. For currents greater than or equal to5 pA, the computed spark amplitudes (F/F-o) are large (similar to6-12 depending on buffer model). We considered several factors that might produce sparks with FWHM similar to2 mum without using large currents. Possible protein-dye interactions increased the FWHM slightly. Hypothetical Ca2+ "quarks" had little effect, as did blurring of sparks by the confocal microscope. A clusters of CRUs, each producing 10 pA simultaneously, can produce sparks with FWHM similar to2 mum. We conclude that cardiac Ca2+ sparks are significantly larger in peak amplitude than previously thought, that such large Ca2+ sparks are consistent with the measured FWHM of similar to2 mum, and that the underlying Ca2+ current is in the range of 10-20 pA.