AJP - Endocrinology and Metabolism, Vol 273, Issue 3 E599-E605, Copyright © 1997 by American Physiological Society
1,25 (OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels
W. Li, R. L. Duncan, N. J. Karin and M. C. Farach-Carson
Department of Basic Science, University of Texas-Houston 77030, USA.
We previously demonstrated electrophysiologically that
1,25-dihydroxyvitamin D3 [1,25(OH)2D3] shifts the activation threshold of
L-type Ca2+ channels in osteoblasts toward the resting potential and
prolongs mean open time. Presently, we used single-cell Ca2+ imaging to
study the combined effects of 1,25(OH)2D3 and parathyroid hormone (PTH)
during generation of Ca2+ transients in fura 2-loaded MC3T3-E1 cells.
Pretreatment with 1,25(OH)2D3 concentrations, which alone did not produce
Ca2+ transients, consistently enhanced Ca2+ responses to PTH. Enhancement
was dose dependent over the range of 1 to 10 nM and was blocked by
pretreatment with 5 microM nitrendipine during pretreatment. A 1,25(OH)2D3
analog that activates L-type channels and shifts their activation threshold
also enhanced PTH responses. In contrast, an analog devoid of membrane Ca2+
effects did not enhance PTH-induced Ca2+ transients. The PTH-induced Ca2+
transient involved activation of a dihydropyridine-insensitive cation
channel that was inhibited by Gd3+. Together, these data suggest that
1,25(OH)2D3 increases osteoblast responsiveness to PTH through rapid
modification of L-type Ca2+ channel gating properties, whose activation
enhances Ca2+ entry through other channels such as the PTH-responsive,
Gd(3+)-sensitive cation channel.
