Thirty years of Ca spark research: digital principle of cell signaling unveiled.

Calcium ions (Ca) are an archetypical and most versatile second messenger in virtually all cell types. Inspired by the discovery of Ca sparks in the 1990s, vibrant research over the last three decades has unveiled a constellation of Ca microdomains as elementary events of Ca signaling and, more importantly, a digital-analog dualism as the system design principle of Ca signaling. In this brief review, we present a sketchy summary on advances in the field of sparkology, and discuss how the digital subsystem can fulfill physiological roles otherwise impossible for any analog system. In addition, we attempt to address how the digital-analog dualism endows the simple cation messenger with signaling speediness, specificity, efficiency, stability, and unparalleled versatility.