Using conventional two-microelectrode voltage-clamp techniques we studied the effects of inorganic mercury (HgCl2) on acetylcholine-, carbachol-, and glutamate-activated currents on Aplysia neurons. Hg2+ was applied with microperfusion. 2. Acetylcholine and carbachol activated an inward, sodium-dependent current in the anterior neurons of the pleural ganglion. The medial neurons gave a biphasic current to acetylcholine and carbachol, which was outward at resting membrane potential. The faster component was Cl- dependent and reversed at about -60 mV, while the slower component was K+ dependent and reversed at greater than -80 mV. 3. Hg2+ (0.1-10 microM) caused a dramatic increase in the acetylcholine- and carbachol-induced inward current in anterior neurons and the fast Cl- current in medial neurons. With only a 1-min preapplication of Hg2+, the acetylcholine- or carbachol-activated sodium or chloride currents were increased to 300% and the effect was only partly reversible. The threshold concentration was 0.1 microM Hg2+. 4. Contrary to the effects on sodium and chloride currents, concentrations of 0.1-10 microM Hg2+ caused a complete and irreversible blockade of K(+)-dependent acetylcholine and carbachol currents. The block of the potassium current was relatively fast and increased with time. The concentration of HgCl2 that gave a half-maximal blockade of the carbachol-activated potassium current was 0.89 microM. The chloride-dependent current elicited by glutamate on medial neurons was increased by HgCl2 as well. 5. These results suggest that actions at agonist-activated channels must be considered as contributing to mercury neurotoxicity. It is possible that the toxic actions of Hg2+ on synaptic transmission at both pre- and postsynaptic sites are important factors in the mechanism of Hg2+ toxicity.
