Calcium regulation in vertebrates: An overview

Abstract

All cells maintain the calcium concentration of their cytoplasm below that of the surrounding fluids. In resting eucaryotic cells the cytoplasmic calcium activity is less than 1 /*M and although there have been no direct measurements in procaryotes, indirect evidence suggests that here too it may be less than 1 PM (Ordal, 1977). Why should Ca2+ be maintained at such a low concentration m all cells? The answer may ultimately derive from the very low solubility of calcium phosphates in water. The phosphatedominated energy economy of cells is of very ancient origin and, at neutral pH, is incompatible with high concentrations of calcium (Kretsinger, 1977). The maintenance of a low intracellular calcium concentration must, therefore, have long been of paramount importance. Cells have the capacity to regulate their internal calcium concentration and, in many cases, they can restore it to normal after periods of rapid calcium entry. It, therefore, seems unlikely that the resting cytoplasmic calcium activity would be directly affected by modest changes in the calcium concentration of extracellular fluids. Nevertheless, it is unclear to what extent precise intracellular calcium homeostasis is dependent on a stable extracellular calcium concentration (Bronner, 1982). In mammals, even small changes in plasma calcium concentration can be deleterious. Hypocalcaemia, for example, causes neuromuscular hyperexcitabihty which seems to result from an extracellular effect of calcium on membrane resistance (Frankenhaeuser and Hodgkin, 1957). Changes in extracellular calcium concentration also substantially affect the responses of cells to agonists that gate calcium, for example, glucosestimulated insulin release from pancreatic islets (Curry et al., 1968). Although the resting cell may be able to regulate its cytoplasmic calcium activity despite changes in plasma calcium, the extracellular and second messenger functions of calcium require that the plasma calcium concentration is stable. For some marine invertebrates that stability is provided by a