• DOI:10.1073/pnas.032427999
• Corpus ID: 30262726

Calcium signaling: A tale for all seasons

@article{Carafoli2002CalciumSA,
  title={Calcium signaling: A tale for all seasons},
  author={Ernesto Carafoli},
  journal={Proceedings of the National Academy of Sciences of the United States of America},
  year={2002},
  volume={99},
  pages={1115 - 1122}
}

• E. Carafoli
• Published 5 February 2002
• Biology
• Proceedings of the National Academy of Sciences of the United States of America

An experiment performed in London nearly 120 years ago, which by today's standards would be considered unacceptably sloppy, marked the beginning of the calcium (Ca2+) signaling saga. Sidney Ringer [Ringer, S. (1883) J. Physiol. 4, 29–43] was studying the contraction of isolated rat hearts. In earlier experiments, Ringer had suspended them in a saline medium for which he admitted to having used London tap water, which is hard: The hearts contracted beautifully. When he proceeded to replace the tap water with distilled water, he made a startling finding: The beating of the hearts became progressively weaker, and stopped altogether after about 20 min. To maintain contraction, he found it necessary to add Ca2+ salts to the suspension medium. Thus, Ringer had serendipitously discovered that Ca2+, hitherto exclusively considered as a structural element, was active in a tissue that has nothing to do with bone or teeth, and performed there a completely novel function: It carried the signal that initiated heart contraction. It was a landmark observation, which should have immediately aroused wide interest. Unexpectedly, however, for decades it attracted no particular attention. Occasionally, farsighted pioneers argued forcefully for a messenger role of Ca2+, offering compelling experimental evidence. Among them, one could quote L. V. Heilbrunn [Heilbrunn, L. V. (1940) Physiol. Zool. 13, 88–94], who contracted frog muscle fibers by applying Ca2+ salts to their cut ends, but not to their surfaces. Heilbrunn correctly concluded that Ca2+ had diffused from the cut ends to the internal contractile elements to elicit their contraction. One could also quote K. Bailey [Bailey, K. (1942) Biochem. J. 36, 121–139], who showed that the ATPase activity of myosin was strongly activated by Ca2+ (but not by Mg2+), and concluded that the liberation of Ca2+ in the neighborhood of the myosin controlled muscle contraction. Clearly, enough evidence was there, but only a handful of people had the vision to see it and to foresee its far-reaching implications. Perhaps no better example of clairvoyance can be offered than the quip by O. Loewy in 1959: “Ja Kalzium, das ist alles!”