1,25 (OH)2D3 enhances PTH-induced Ca2+ transients in preosteoblasts by activating L-type Ca2+ channels.
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.
Li
W
W
Department of Basic Science, University of Texas-Houston 77030, USA.
Duncan
R L
RL
Karin
N J
NJ
Farach-Carson
M C
MC
D016475:3T3 Cells; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002454:Cell Differentiation; D004357:Drug Synergism; D005682:Gadolinium / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013997:Time Factors
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010281:Parathyroid Hormone; D005682:Gadolinium; D002117:Calcitriol; D002118:Calcium