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It is now clearer and clearer that mitochondria play a role, and perhaps an active role, in cell calcium signalling. The fact that mitochondria can exhibit a Ca2+-induced Ca2+ release (mCICR, Ichas et al. [37]) reinforces this concept and makes the mitochondria an essential element in the relay of Ca2+ wave propagation. It must be emphasized that the modulation of cell Ca2+ signals by mitochondria depends upon their energetic status, thus making mitochondria an essential link between energy metabolism and calcium signalling inside the cell.(Mol Cell Biochem 184: 371–376, 1998)

Both genetic and environmental factors are usually considered to play interacting roles in the pathogenesis of human disease. Scant attention, however, has been paid to the possible role that evolutionary events may play in health and disease. Life on this planet began in an anaerobic atmosphere and in a sea rich in K+, Mg2+,and phospate, but low in Na + and Ca2+, these new extracellular ions became the means of providing the cell with two major new attributes: the property of excitability of its surface membrane (the Na+ gradient), and the ability to couple events occurring at this surface membrane to the metabolic events within the cell (the calcium messenger).

Hypothermic chemical cardioplegia is currently used by most cardiac surgeons for the preservation of globally ischaemic myocardium of open-heart surgery. This technique involves aortic cross-clamping and the resultant effects of global ischaemic arrest are minimised by intracoronary infusion of cold chemical cardioplegic solutions. 1–4 These procedures offer a certain degree of myocardial metabolic and cellular preservation during prolonged periods of ischaemia. However, there is still some concern about the relative merits or otherwise of hypothermic cardioplegic myocardial preservation. 3 The major emphasis of most experimental and clinical studies has been preservation of high energy phosphates as the measure of effectiveness of hypothermic cardioplegia. 2 Cellular Ca2+ kinetics has attracted little attention although derangement in calcium homeostasis is the eventual determinant of ischaemia-induced cellular necrosis. 5

Our knowledge of the biological importance of calcium began about a century ago with the serendipitous discovery made by Sydney Ringer that a solution of sodium chloride plus tap water was more efficacious in maintaining cardiac contractility than a corresponding one constituted from distilled water [23]. Ringer concluded that the minute amount of calcium present in tap water antagonized the “injurious” effects of sodium. Locke and other investigators subsequently demonstrated that motor nerves exposed to pure sodium chloride lose their stimulant effects on muscle contractility which could be restored by adding calcium (and potassium) in the proper proportions [25]. So, by the early 20th century researchers had become well aware that normal biological activity depended on specific concentrations of calcium, sodium, and potassium, with calcium occupying a key position in the natural order of things.