Spatiotemporal features of Ca2+ buffering and diffusion in atrial cardiac myocytes with inhibited sarcoplasmic reticulum
Spatiotemporal features of Ca2+ buffering and diffusion in atrial cardiac myocytes with inhibited sarcoplasmic reticulum
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DOI：
10.1016/s0006-3495(02)75317-4
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发表时间：
2002-12-01
影响因子：
3.4
通讯作者：
Niggli, E
中科院分区：
文献类型：
--
作者：
Michailova, A;DelPrincipe, F;Niggli, E
细胞中的Ca 2+信号传导主要受Ca 2+扩散和Ca 2+与移动的和固定的Ca 2+缓冲液（包括细胞器）的结合控制。为了研究心脏心房肌细胞中的Ca 2+信号，开发了一个Ca 2+扩散的数学模型，该模型代表了几个亚细胞隔室，包括具有受限扩散的肌膜下空间、肌丝空间和胞质溶胶。该模型被用来定量模拟实验Ca 2+信号的幅度，时间过程和空间特征。作为实验参考数据，用全细胞电压钳技术记录心房肌细胞L-型Ca ~（2+）电流。Ca 2+信号用荧光Ca 2+指示剂Fluo-3和激光扫描共聚焦显微镜同时成像。模拟结果表明，在心房肌细胞缺乏T-小管，Ca 2+运动从细胞膜到细胞的中心强烈依赖于存在的移动的Ca 2+缓冲，特别是当肌浆网被抑制后。此外，在涌入的Ca 2+大和陡峭的浓度梯度之间的胞质溶胶和submicroscopically狭窄的subsarcolemmal空间预测。此外，计算结果显示，尽管ATP的Ca 2+亲和力较低，但即使在Ca 2+内流期间达到[Ca 2 +]（i）的适度升高时，ATP也可作为Ca 2+的重要缓冲液和载体。
Ca2+ signaling in cells is largely governed by Ca2+ diffusion and Ca2+ binding to mobile and stationary Ca2+ buffers, including organelles. To examine Ca2+ signaling in cardiac atrial myocytes, a mathematical model of Ca2+ diffusion was developed which represents several subcellular compartments, including a subsarcolemmal space with restricted diffusion, a myofilament space, and the cytosol. The model was used to quantitatively simulate experimental Ca2+ signals in terms of amplitude, time course, and spatial features. For experimental reference data, L-type Ca2+ currents were recorded from atrial cells with the whole-cell voltage-clamp technique. Ca2+ signals were simultaneously imaged with the fluorescent Ca2+ indicator Fluo-3 and a laser-scanning confocal microscope. The simulations indicate that in atrial myocytes lacking T-tubules, Ca2+ movement from the cell membrane to the center of the cells relies strongly on the presence of mobile Ca2+ buffers, particularly when the sarcoplasmic reticulum is inhibited pharmacologically. Furthermore, during the influx of Ca2+ large and steep concentration gradients are predicted between the cytosol and the submicroscopically narrow subsarcolemmal space. In addition, the computations revealed that, despite its low Ca2+ affinity, ATP acts as a significant buffer and carrier for Ca2+, even at the modest elevations of [Ca2+](i) reached during influx of Ca2+.