DUAL MODULATION OF THE L-TYPE CALCIUM CURRENT OF RAT OSTEOBLASTIC CELLS BY PARATHYROID-HORMONE - OPPOSITE EFFECTS OF PROTEIN-KINASE-C AND CYCLIC-NUCLEOTIDES

Using whole-cell voltage-clamp recording of rat osteoblastic cells, we show that PTH-(1-34), known to stimulate protein kinase C (PKC) and adenylate cyclase, has a dual effect on the L-type calcium current. It induces a long-lasting increase and a superimposed reversible decrease, which can be separated by repeating hormone applications. The stimulatory effect is the only effect induced by the (3-34) fragment, able to stimulate PKC but unable to stimulate adenylate cyclase. The L current is stimulated by an active phorbol ester and is reduced by permeable analogues of cyclic AMP. Thus, the effect of PTH-(1-34) can be explained by the opposite effects of PKC and cyclic AMP. Dibutyryl cyclic GMP reduces the L current even more potently than dibutyryl cyclic AMP. The above modulations are all voltage-insensitive. These results led us to reinvestigate the effects of some vitamin D-3 metabolites known to stimulate PKC and/or guanylate cyclase, and previously reported to affect the voltage-sensitivity of the L current. We only detected voltage-insensitive effects.