Ca 2+ Nanosparks

Since the classical, many years ignored, and by current standards haphazard experiments of Sidney Ringer1 on isolated rat hearts, we have come a long way in understanding the role of Ca2+ in the contraction of cardiac muscle. Ringer1 found that suspending the hearts in a saline solution prepared with tap water (which contained high amounts of calcium carbonate from limestone) sustained robust contractions for a long time; but in an attempt to professionalize his art, Ringer1 replaced tap water for distilled water, only to observe that in this clean medium, heart contractions declined quickly after only a few beats. By systematically adding different salts to the distilled saline medium, Ringer1 discovered that calcium, until then considered exclusively a structural element of bones and teeth, was essential for cardiac muscle contraction. Since this serendipitous discovery, many others, in smaller or greater scale, kept adding to the inescapable notion that calcium ions (Ca2+) play a critical role as a relay signal (a messenger) in many biological processes not only of cardiac myocytes, but also of virtually every living cell. Continuing with the story of Ca2+ in the heart, technically challenging experiments by Alexander Fabiato2 defined, almost singlehandedly, the process of Ca2+-induced Ca2+ release in cardiac cells, whereby a small amount of Ca2+ (in his case injected by a microsyringe on skinned cardiac tissue) caused a much larger release of Ca2+ from the sarcoplasmic reticulum (SR), inducing vigorous contractions. Fabiato’s experiments, therefore, set the basis for a functional coupling between the sarcolemma (and its invaginations, the t-tubules) which injected Ca2+ by the voltage-induced opening of L-type Ca2+ channels (dihydropyridine receptors [DHPRs]) and the SR, which elicited massive Ca2+ release on binding of the incoming Ca2+ to …