Effect of tri-n-butyltin on NMDA-induced currents in rat CNS neurons

The effect of tri-n-butyltin (TBT), an antifouling agent, on NMDA-induced currents was investigated in neurons acutely dissociated from rat dorsal motor nucleus of the vagus by the use of nystatin-perforated patch recording configuration under the voltage-clamp conditions. The application of 10^-4 M NMDA induced a peak inward currnt which was followed by a steady state current, and an outward current immediately after washout at a holding potential of -40 mV. TBT markedly potentiated the NMDA-induced outward current, although it had no significant effect on the inward currents. The reversal potential of the NMDA-induced outward current was 79 mV, which was close to the theoretical K^+ equilibrium potential. The NMDA-induced outward current was blocked by charybdotoxin, suggesting contribution of Ca^2+ -activated large conductance K^+ channels. Removal of extracellular Ca^2+ and pre-treatment of BAPTA-AM, a membrane permeable Ca^2+ -chelator, inhibited the NMDA -induced outward currents. These results suggest that TBT did not affect the NMDA-induced Ca^2+ influx into the neurons, but it inhibited Ca^2+ clearance by affecting the Ca^2+ efflux to the extracellualr space and/or reuptake into the intracellular Ca^2+ stores.