Origins of Ca Imaging with Fluorescent Indicators.

In 1980, Roger Tsien published a paper, in this journal [Tsien, R. Y. (1980) , (11), 2396], titled "New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures". These new buffers included 1,2-bis(-aminophenoxy)ethane-,,','-tetraacetic acid, or BAPTA, which is still widely used today. And so, the world was set alight with new ways in which to visualize Ca. The ability to watch fluctuations in intracellular Ca revolutionized the life sciences, although the fluorescent indicators used today, particularly in neurobiology, no longer rely exclusively on BAPTA but on genetically encoded fluorescent Ca indicators. In this Perspective, we reflect on the origins of Ca imaging with a special focus on the contributions made by Roger Tsien, from the early concept of selective Ca binding described in to optical Ca indicators based on chemically synthesized fluorophores to genetically encoded fluorescent Ca indicators.