Part of “CHAPTER 49 – PHYSIOLOGY OF CALCIUM METABOLISM“

Calcium ions (Ca²⁺) play numerous critical roles in both intra-cellular and extracellular physiology (Table 49-1). Intracellular Ca²⁺ is an important regulator of a variety of cellular functions, including processes as diverse as muscle contraction, hormonal secretion, glycogen metabolism, and cell division.1,2 and 3 Many of these functions are accomplished through the interaction of Ca²⁺ with intracellular binding proteins, such as calmodulin, which then activate enzymes and other intracellular effectors.2,3 The cytosolic free calcium concentration in resting cells is ˜100 nmol/L. It is regulated by channels, pumps, and other transport mechanisms that control the movements of Ca²⁺ into and out of cells and between various intracellular compartments.1,2 and 3 Consonant with its role as a key intracellular second messenger, the cytosolic free Ca²⁺ concentration (Ca_i) can rise by as much as 100-fold (i.e., to 1–10 μmol/L) during cellular activation. Such increases in Ca_i are the result of uptake of extracellular Ca²⁺ through Ca²⁺-permeable channels in the plasma membrane, release of Ca²⁺ from its intra-cellular stores, such as the endoplasmic reticulum, or both factors. Despite the importance of intracellular Ca²⁺ in cellular metabolism, this compartment comprises only 1% of total body calcium.4

In contrast to intracellular Ca²⁺ concentration, the extracellular free Ca²⁺ concentration (Ca²⁺_o) is ˜1 mmol/L. It is closely regulated by a complex homeostatic system involving the parathyroid hormone (PTH)–secreting parathyroid glands and calcitonin-secreting thyroidal C cells as well as specialized Ca²⁺-transporting cells in the intestine, skeleton, and kidney.4,5,6 and 7 This system regulates the flow of Ca²⁺ into and out of the body as well as between various bodily compartments, particularly between the skeleton and extracellular fluid. The rigid control of Ca²⁺_o ensures a steadysupply of Ca²⁺ for vital intracellular functions. Ca²⁺_o has otherimportant roles, such as maintaining intercellular adhesion, promoting the integrity of the plasma membrane, and ensuring the clotting of blood, which further emphasizes the importance of maintaining near constancy of Ca²⁺_o. The total amount of soluble extracellular calcium, however, like intracellular Ca²⁺, constitutes only a minute fraction of total bodily Ca²⁺ (˜0.1%; see Table 49-1). Most of the Ca²⁺ within the body (>99%) resides as calcium phosphate salts within the skeleton, where it serves two important functions. First, it protects vital internal organs and acts as a rigid framework that facilitates locomotion and other bodily movements. Second, it provides a nearly inexhaustible reservoir of calcium and phosphate ions for times of need when intestinal absorption and renal conservation are insufficient to maintain adequate levels of these ions within the extracellular fluid.