24,25(OH)2 vitamin D3 modulates the L-type Ca2+ channel current in UMR 106 cells: involvement of protein kinase A and protein kinase C.
In this study, the effect of 24,25(OH)2 vitamin D3 (24,25D3), on the L-type Ca2+ channel current (L-channel current) in UMR 106 cells was investigated using the whole cell version of the patch clamp technique. It was found that 24,25D3 had a dual effect on the L-channel current: a low concentration of 24,25D3 (1 x 10(-8) M) increased the amplitude of the L-channel current by 49 +/- 11%, whereas a high concentration of 24,25D3 (1 x 10(-5) M) reduced the amplitude of the current by 55 +/- 7%. The effect of a low concentration of 24,25D3 was mimicked by 8-bromo-cAMP and inhibited by Rp-cAMPs, indicating the involvement of the cAMP/protein kinase A pathway. In contrast, the effect of a high concentration of 24,25D3 was mimicked by 4 beta-phorbol 12-myristate 13-acetate and inhibited by calphostin C, indicating the involvement of protein kinase C. In comparison, a high concentration of 1,25(OH)2 vitamin D3 (1,25D3) (1 x 10(-6) M) increased the L-channel current in UMR 106 cells. Therefore, 24,25D3 appears to have an action on the L-channel current that is distinct from that of 1,25D3. This demonstration of a non-genomic effect of 24,25D3 on calcium channels suggests that 24,25D3 is an active metabolite of vitamin D3 and may play an important role in regulating the function of bone cells.
Li
B
B
Department of Physiology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Chik
C L
CL
Taniguchi
N
N
Ho
A K
AK
Karpinski
E
E
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015650:24,25-Dihydroxyvitamin D 3; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate