CALCIUM HOMEOSTASIS - AN OLD PROBLEM REVISITED

This article proposes a novel model of calcium homeostasis, based on t he concept of a series of bone calcium-binding sites of varying calciu m affinities. When an i.v. Ca load is administered to mammals, it is r apidly (t(1/2) < 1 min) dispersed into a volume equivalent to the extr acellular fluid. Thereafter the calcium concentration drops monoexpone ntially with a t(1/2) of tens of minutes. When a negative Ca load is a dministered, as by EDTA injection, the return to the preinjection plas ma Ca level, [Ca-s], occurs also monoexponentially at the same rate as restoration after a positive load. The numerical value of the rate ca n be arrived at by taking into account the fraction of cardiac output (5%) that is directed to the skeleton. Acute regulation is brought abo ut by controlling access to subpopulations of the Ca binding sites, wh ose average K-m determines [Ca-s]. Osteoblasts, when active and extend ed, block low-affinity binding sites; osteoclasts, when active and ext ended, block high-affinity sites. Exposure of sites is brought about w hen bone cells respond by rapid shape changes, osteoblasts rounding up in response to parathyroid hormone (PTH) or vitamin D, osteoclasts ro unding up in response to calcitonin. These shape changes are the first steps in the cascade of events that lead to bone formation and resorp tion, but acute regulation need not involve the latter steps of a casc ade. The model accounts for the changes in the response times to Ca lo ads that have been observed in older animals or those deprived of PTH, calcitonin or vitamin D.