MODIFICATION OF THE ELECTRIC COUPLING BETWEEN OSTEOBLAST-LIKE CELLS BY ANTICONVULSANTS

Anticonvulsants like carbamazepine, phenytoin and phenobarbital may le ad to osteomalacia by unknown mechanisms. In principle, interruption o f the intercellular communication between bone cells mediated by gap j unctions can contribute to these disturbances. In order to study the i nfluence of anticonvulsant drugs on the electric coupling, calvarial f ragments of newborn rats and of guinea pigs were explanted onto collag en-coated coverslips and maintained in primary culture for 2 - 6 weeks . As in vivo cells growing out of the explant (Fig. 1) revealed a stro ng electric coupling measured by parallel intracellular recordings fro m neighbouring cells (Fig. 2). The anticonvulsant drugs carbamazepine (0.1 mmol/l; Fig.3) and phenytoin (0.1 nmol/l; Fig. 4) caused a rapid and reversible reduction of the electric coupling factor to about 2/3 of the original value. Phenobarbital (0.1 or 1 mmol/l, respectively; F ig. 5) reduced the electric coupling in some cell pairs to about 2/3 b ut improved the coupling strength in other cell pairs. Inhibition of i ntercellular communication between osteoblast-like cells as found in v itro by carbamazepine, phenytoin or phenobarbital may contribute to th e above mentioned osseous disease in vivo.