24,25(OH)(2) vitamin D modulates the L-type Ca-3(2+) 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 D-3 (24,25D(3)), 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 24,25D(3) had a dual effect on the L-channel current: a low concentration of 24,25D(3) (1 x 10(-8) M) increased the amplitude of the L-channel current by 49 +/- 11%, whereas a high concentration of 24,25D(3) (1 x 10(-5) M) reduced the amplitude of the current by 55 +/- 7%. The effect of a low concentration of 24,25D(3) 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 24,25D(3) 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 D-3 (1,25D(3)) (1 x 10(-6) M) increased the L-channel current in UMR 106 cells. Therefore, 24,25D(3) appears to have an action on the L-channel current that is distinct from that of 1,25D(3). This demonstration of a non-genomic effect of 24,25D, on calcium channels suggests that 24,25D(3) is an active metabolite of vitamin D-3 and may play an important role in regulating the function of bone cells.