It is now almost one hundred years since Sidney Ringer (1882) described the importance of Ca2+ in the maintenance of frog heart contractility. Subsequent to this observation, it has been increasingly recognized that Ca2+ plays a critical and central role in a multitude of biological events at both the intra-and extracellular levels (Duncan, 1976; Kretsinger, 1976a; Table 1). However, Ca2+ distribution across the cell membrane is far from equilibrium, since if the resting membrane potential (~-60mV) were equal to the Ca2+ equilibrium potential, then the intracellular Ca2+ activity should be some 100-fold greater than the extracellular activity. This is quite clearly not so and although accurate measurements of free ionized intracellular Ca2+ concentrations have not been made in many systems the concensus of evidence firmly indicates that [Ca int 2+ ] < 10-7M (Baker, 1972; 1976; Blaustein, 1974; Reuter, 1973). Such a low intracellular Ca2+ concentration accords with the binding constants of Ca2+ for those intracellular proteins whose activity is known to be modulated by Ca2+ (pKD values ~ 6–7; Kretsinger, 1976a,b) and indicates the “trigger” functipn of an increased intracellular Ca2+ concentration (Heilbrunn, 1956).