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- calcium ATPase
- calcium channels
- calcium signaling
- cellular function
- excitable cells
- reactive oxygen species
- second messengers
How does a person pen 1200 words on “calcium rules” when a search for “calcium” in PubMed produces >530 000 references, 15 000 of which are from 2016 alone? To face this challenge, I decided to recount my life’s journey unveiling some of these rules, a journey that has led me to conclude that this versatile element, so important to the central processes of life, does in fact rule the cell.
I first became acquainted with the calcium ion (Ca2+) in the mid-1960s when I studied Ca2+ efflux from the squid giant axon under the guidance of Eduardo Rojas in Montemar, Chile. In 1968, we reported that this complex process exhibits metabolism-dependent components controlled by mitochondrial function. Squid seasons were short, precluding us from testing, as planned, the effects of removing external sodium (Na+) on Ca2+ efflux. Thus, we missed the discovery of the Na+-Ca2+-exchanger reported in the late 1960s by Reuter and Seitz in cardiac muscle and in the squid axon by Peter Baker and colleagues.
What did we know then about Ca2+ rules? From the pioneering studies of Sydney Ringer, we were aware that heart contraction required Ca2+, but the underlying mechanisms emerged many years later. In the early 1960s, for instance, 3 independent research teams led by Wilhelm Hasselbach in Germany, Setsuro Ebashi in Japan, and Annemarie Weber in the United States reported Ca2+ uptake by the sarcoplasmic reticulum and discovered the sarcoplasmic reticulum calcium pump, later known as the sarco/endoplasmic reticulum calcium ATPase pump. They also showed …