METHYL MERCURY REDUCES VOLTAGE-ACTIVATED CURRENTS OF RAT DORSAL-ROOT GANGLION NEURONS

Methyl mercury (MeHg) is a widespread toxicant with major actions on t he nervous system. Since the function of neurons depends on voltage ga ted ion channels, we examined the effects of micromolar concentrations of methyl mercury on voltage-activated calcium, potassium and sodium channel currents of cultured rat dorsal root ganglion (DRG) neurons. T he cells, which were obtained from 2-4 day old rat pups, were whole-ce ll patch-clamped. Currents were separated by selective intra- and extr acellular solutions as well as specific depolarizing voltage steps. We did not distinguish between different calcium, potassium or sodium ch annel subtypes. All three types of voltage-activated currents were irr eversibly reduced by MeHg in a concentration dependent manner. Voltage -activated calcium and potassium channel currents were more sensitive to MeHg (Calcium: IC50 = 2.6+/-0.4 mu M; Potassium: IC50 = 2.2+/-0.3 m u M) than voltage-activated sodium channels (IC50 = 12.3+/-2.0 mu M) T he Hill coefficients for the reduction of the currents were calculated as similar to 1 for calcium and potassium channel currents and as 1.7 for sodium currents. In the cases of the voltage-activated calcium an d sodium channel currents the reduction was clearly use dependent. Hig her concentrations of MeHg (greater than or equal to 5 mu M) resulted in a biphasic change in the holding membrane current at the potential of -80 mV in similar to 25% of the cases.