Modulation of bone calcium-binding sites regulates plasma calcium: an hypothesis.
A new model of calcium (Ca) homeostasis is proposed. It is based on the kinetics of restoration of the plasma Ca level following positive or negative Ca loads in animals of different endocrine status. As others, we can account for the kinetics of plasma Ca restoration as being the result of a very rapid dilution of Ca into extracellular water (t1/2 less than 1 minute) and an uptake or release by bone (t1/2 = 14-80 minutes) that occurs as the fraction of cardiac output directed to bone is partially cleared of or repleted with Ca. In this model, bone surfaces have Ca-binding sites that demonstrate a range of affinities and whose average Km determines the plasma Ca level. Acute regulation is brought about by controlling access to subpopulations of Ca binding sites in bone, comprising the extremes of high and low affinity. Osteoblasts, when active and extended, block the low affinity sites, and osteoclasts, when active and extended, block the high affinity sites. Exposure of low- or high-affinity sites is brought about when these cells respond to hormonal signals by contraction, parathyroid hormone (PTH), and vitamin D leading to osteoblast, and calcitonin to osteoclast, contraction. These reciprocal cell shape changes are the first in a cascade of metabolic events that lead to bone formation and resorption, as well as changes in the number or affinity of the binding sites. The model also accounts for the prolongation of the response time to Ca loads in animals deprived of PTH, calcitonin, or vitamin D.
Bronner
F
F
Department of BioStructure and Function, University of Connecticut Health Center, Farmington 06030.
Stein
W D
WD
D000818:Animals; D001665:Binding Sites; D001842:Bone and Bones / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000097:blood* / Q000378:metabolism; D006706:Homeostasis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D014807:Vitamin D / Q000494:pharmacology
D010281:Parathyroid Hormone; D014807:Vitamin D; D002116:Calcitonin; D002118:Calcium