Calcium homeostasis--an old problem revisited.
This article proposes a novel model of calcium homeostasis, based on the concept of a series of bone calcium-binding sites of varying calcium affinities. When an i.v. Ca load is administered to mammals, it is rapidly (t1/2 < 1 min) dispersed into a volume equivalent to the extracellular fluid. Thereafter the calcium concentration drops monoexponentially with a t1/2 of tens of minutes. When a negative Ca load is administered, as by EDTA injection, the return to the preinjection plasma Ca level, [Cas], occurs also mono-exponentially at the same rate as restoration after a positive load. The numerical value of the rate can be arrived at by taking into account the fraction of cardiac output (5%) that is directed to the skeleton. Acute regulation is brought about by controlling access to subpopulations of the Ca binding sites, whose average Km determines [Cas]. Osteoblasts, when active and extended, block low-affinity binding sites; osteoclasts, when active and extended, block high-affinity sites. Exposure of sites is brought about when bone cells respond by rapid shape changes, osteoblasts rounding up in response to parathyroid hormone (PTH) or vitamin D, osteoclasts rounding up in response to calcitonin. These shape changes are the first steps in the cascade of events that lead to bone formation and resorption, but acute regulation need not involve the latter steps of a cascade. The model accounts for the changes in the response times to Ca loads that have been observed in older animals or those deprived of PTH, calcitonin or vitamin D.
Bronner
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Department of BioStructure and Function, University of Connecticut Health Center, Farmington 06030-3705, USA.
Stein
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WD
D000818:Animals; D001665:Binding Sites; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D008954:Models, Biological; D010281:Parathyroid Hormone / Q000494:pharmacology
D010281:Parathyroid Hormone; D002116:Calcitonin; D002118:Calcium