METHYLMERCURY INHIBITS GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN PRIMARY CULTURES OF RAT PROXIMAL TUBULAR CELLS

Methylmercury(MeHg) causes renal injury in addition to central and per ipheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg , we investigated the effect of this compound on intercellular communi cation through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 mu M MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxi city. When the medium containing MeHg was exchanged with MeHg-free med ium, dye coupling recovered abruptly. However, the dye-coupling was ab olished again 30 min after replacement with control medium, and the ce lls were damaged. Intracellular calcium concentration, [Ca2+](i), whic h modulates the function of gap junctions, significantly increased fol lowing exposure of the cells to 30 mu M MeHg and returned to control l evel following replacement with MeHg-free medium. These results sugges t that the inhibiting effect of MeHg on GJIC is related to the change in [Ca2+](i), and may be involved in the pathogenesis of renal dysfunc tion.