Local control of Ca2+-induced Ca2+ release in mouse sinoatrial node cells.
Local control of Ca2+-induced Ca2+ release in mouse sinoatrial node cells.
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DOI：
10.1016/j.yjmcc.2009.07.007
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发表时间：
2009-11
影响因子：
5
通讯作者：
Song, Long-Sheng
中科院分区：
文献类型：
--
作者：
Chen, Biyi;Wu, Yuejin;Mohler, Peter J.;Anderson, Mark E.;Song, Long-Sheng
来自大型动物模型的新证据表明，Ca 2+调节，特别是细胞内肌浆网（SR）Ca 2+释放，对窦房结（SAN）自律性至关重要。然而，尽管SR Ca 2+释放对SAN细胞功能的明显重要性，但尚不确定小鼠SAN细胞中SR Ca 2+释放是如何控制的。了解小鼠SAN SR Ca 2+释放机制将有助于更好地理解Ca 2+稳态蛋白遗传小鼠模型对SAN的研究结果。本研究采用膜片钳电流记录和高分辨率共聚焦钙离子成像技术，在单个SAN细胞水平上研究了肌膜钙内流和SR钙释放之间的功能关系。在小鼠SAN细胞中，Ca 2+通道电流和触发SR Ca 2+瞬变均显示钟形，与膜电位的分级功能。此外，Ca 2 +-诱导的Ca 2+释放（CICR）的增益函数显示了一个单调递减的功能，具有很强的电压依赖性，与CICR的“本地控制”机制。此外，我们观察到许多离散的Ca 2+火花在舒张期去极化的电压范围内，在静息电位观察到的火花的频率低得多形成鲜明对比。我们得出结论，CICR的“局部控制”机制负责舒张期去极化过程中的局部Ca 2+释放和SAN细胞动作电位过程中观察到的同步Ca 2+瞬变。
Emerging evidence from large animal models implicates Ca2+ regulation, particularly intracellular sarcoplasmic reticulum (SR) Ca2+ release, as essential for sinoatrial node (SAN) automaticity. However, despite the apparent importance of SR Ca2+ release to SAN cell function it is uncertain how SR Ca2+ release is controlled in SAN cells from mouse. Understanding mouse SAN SR Ca2+ release mechanism will allow improved understanding of results in studies on SAN from genetic mouse models of Ca2+ homeostatic proteins. Here we investigated the functional relationship between sarcolemmal Ca2+ influx and SR Ca2+ release at the level of single SAN cell, using simultaneous patch-clamp current recording and high resolution confocal Ca2+ imaging techniques. In mouse SAN cells, both Ca2+ channel currents and triggered SR Ca2+ transients displayed bell-shaped, graded function with the membrane potential. Moreover, the gain function for Ca2+-induced Ca2+ release (CICR) displayed a monotonically decreasing function with strong voltage-dependence, consistent with a ‘local control’ mechanism for CICR. In addition, we observed numerous discrete Ca2+ sparks at the voltage range of diastolic depolarization, in sharp contrast to the much lower frequency of sparks observed at resting potentials. We concluded that the ‘local control’ mechanism of CICR is responsible for both local Ca2+ release during diastolic depolarization and the synchronized Ca2+ transients observed during action potential in SAN cells.
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