钙火花研究进展与瞻望

CALCIUM SPARKS AND CALCIUM SIGNALING IN HEART

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"数-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。

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.