In the late 1960s, micro injections of giant muscle cells with aequorin, a Ca2+-triggered bioluminescent protein, gave rise to the first measurements of cytosolic free calcium in living cells. Though partially eclipsed for some years, this old molecule is again up to date thanks to chemistry and molecular biology techniques, for detection of Ca2+ hot spots and measurement of intra-organelles Ca2+ concentrations. In 1982, Tsien introduced a new generation of fluorescent Ca+2 chelators, derivated from EGTA, and conceived a chemical trick (acetoxymethyl esterification) for loading them by a non-disruptive way into populations of cells of any size. Today, the recent development of highly fluorescent Ca2+ specific probes (Fura2, Indol, and more recently, Fluo3, Fura red, etc.), coupled with advances in microscopy, computer and video imaging technologies, allows a breakthrough in the understanding of Ca2+ homeostasis, making this field one of the most exciting and rapidly evolving of cell biology.
