钙火花研究进展与瞻望

钙离子是最广泛而又最重要的细胞内第二信使。自1993年以来，钙火花等一系列钙信号基本单元相继发现，揭示了细胞钙信号转导的数字-模拟二元特征：纳米-微米尺度上短暂的钙信号事件（数字系统）随机叠加于连续的全细胞钙信号（模拟系统）背景中。数字模式的微区域钙信号赋予细胞钙信号在时间、空间、幅度上多尺度多层次的精细结构。对钙火花激活机制、协同机制、终止机制等方面的研究，为钙释放通道阵列的门控及调节提出了新的见解和问题。钙火花等对于高域值钙依赖性过程（如肌细胞兴奋-收缩耦联、细胞兴奋性和神经细胞分泌）的激活和时空调控具有特别重要的生理和病理意义。钙信号“激-模二元性”的研究可望进一步揭示细胞钙信号的简单性与复杂性的统一。

CALCIUM SPARKS AND CALCIUM SIGNALING IN HEART

The calcium ion (Ca2+) is the simplest and the most versatile intracellular second messenger known to date. Over last decade, the discovery of Ca2+ sparks and a family of local elementary Ca2+ signaling events has unveiled a “digital-analog” feature of intracellular Ca2+ signaling. Brief, local “digital” Ca2+ microdomains and nanodomains are commingled with the continuous global “analog” Ca2+ signals. Patterned activation of digital Ca2+ signals confers on intracellular Ca2+ signaling a multi-scaled architecture in space, time and magnitude, and is of particular relevance in spatiotemporal regulation of high-threshold Ca2+-dependent processes (e.g., striated muscle excitation-contraction coupling, exocytosis). Investigation on spark activation, coordination, and termination has revealed new insights as well as perplexing questions about gating of Ca2+ release channels (ryanodine receptor, inositol 1,4,5-trisphosphate receptor) in intact cells, and brought about mechanistic understanding of the diverse and even opposing roles of Ca2+ signaling. Future investigation on “digital-analog” dichotomy of Ca2+ signaling thus holds the promise to unify the simplicity and complexity of Ca2+ signaling in biology.