Thirty years of Ca²⁺ spark research: digital principle of cell signaling unveiled

Abstract

Calcium ions (Ca²⁺) are an archetypical and most versatile second messenger in virtually all cell types. Inspired by the discovery of Ca²⁺ sparks in the 1990s, vibrant research over the last three decades has unveiled a constellation of Ca²⁺ microdomains as elementary events of Ca²⁺ signaling and, more importantly, a digital-analog dualism as the system design principle of Ca²⁺ 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.

Graphical abstract

Keywords

Ca²⁺ signaling / Ca²⁺ microdomain / Digital system design

Acknowledgements

We are grateful to Drs. L.S. Song and S.Q. Wang for valuable discussions on the concepts presented in this work. We are also in debt to our collaborators, colleagues and students whose collective contribution has laid the foundation of the field of sparkology. This work is supported by the National Natural Science Foundation of China (32293211, 61972009, 92157105, 81827809) (to HC) and JIH1340085Y (to FL).

RIGHTS & PERMISSIONS

2024 The Author(s)