The Multiple Physiological Roles of Calcium: Possible Sites for Pharmacological Intervention

Abstract

It is not at all surprising that calcium is an important constituent of living cells since it is one of the more readily available elements, comprising some 3.6% of the lithosphere. Furthermore evidence for the most ancient forms of life comes from the algal limestones of Central Africa, which are apparently 2.7 × 10⁹ years old (Oparin 1969). In one of the earliest symposia on the cellular functions of calcium, the late Peter Baker made some remarks which are just as pertinent today as they were in 1970. At that time the first estimates of the intracellular ionised calcium concentration were being made both by direct measurement, using aequorin, and indirectly, by using calcium buffer systems. It was discovered that muscle contraction required the intracellular ionised calcium concentration to rise to the micromolar range and that resting levels were perhaps only one tenth of this value. Baker pointed out that most cells would accumulate calcium if this was dependent only upon the Donnan ratio. Further with intracellular potentials of around — 60 mV and an external calcium concentration of 1–10 mM, intracellular concentrations of 0.1–1.0 M could be expected. Clearly this was not the case; living cells had developed a variety of mechanisms to keep the intracellular ionised calcium at very low values indeed. Given this scenario transient increases in intracellular ionised calcium might then act as a trigger for a variety of cellular functions and these functions would be terminated by the activities which maintained the normal resting low level of intracellular calcium ions.