1,25(oh)2d3 enhances parathyroid hormone-induced ca2+ transients in
pre-osteoblasts by activating l-type ca2+ channels.
Li, Wei, Randall L. Duncan, Norman J. Karin, and Mary C. Farach
-Carson.
Department of Basic Science, University of Texas- Houston, Dental
Branch, Houston, TX 77030, Department of Orthopaedic Surgery, Indiana
University Medical Center, Indianapolis, IN 46202
APStracts 4:0118E, 1997.
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. Pre-treatment 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 1-10 nM, and
blocked by pre-treatment with 5 [mu]M nitrendipine during pre
-treatment. 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, Gd3+
-sensitive cation channel.
Received 1997 January 27; accepted in final form 1997 May 21
APS Manuscript Number E038-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 11 June 1997