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

Anticonvulsants like carbamazepine, phenytoin and phenobarbital may lead to osteomalacia by unknown mechanisms. In principle, interruption of the intercellular communication between bone cells mediated by gap junctions can contribute to these disturbances. In order to study the influence of anticonvulsant drugs on the electric coupling, calvarial fragments of newborn rats and of guinea pigs were explanted onto collagen-coated coverslips and maintained in primary culture for 2 - 6 weeks. As in vivo cells growing out of the explant (Fig. 1) revealed a strong electric coupling measured by parallel intracellular recordings from 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; Fig. 5) reduced the electric coupling in some cell pairs to about 2/3 but improved the coupling strength in other cell pairs. Inhibition of intercellular communication between osteoblast-like cells as found in vitro by carbamazepine, phenytoin or phenobarbital may contribute to the above mentioned osseous disease in vivo.