EFFECT OF HGCL2 ON ACETYLCHOLINE CARBACHOL AND GLUTAMATE CURRENTS OF APLYSIN NEURONS

1. Using conventional two-microelectrode voltage-clamp techniques we s tudied the effects of inorganic mercury (HgCl2) on acetylcholine-, car bachol-, 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 pl eural ganglion. The medial neurons gave a biphasic current to acetylch oline and carbachol, which was outward at resting membrane potential. The faster component was Cl- dependent and reversed at about -60 mV, w hile the slower component was K+ dependent and reversed at greater tha n -80 mV. 3. Hg2+ (0.1-10 mu M) caused a dramatic increase in the acet ylcholine- and carbachol-induced inward current in anterior neurons an d the fast Cl- current in medial neurons. With only a 1-min preapplica tion of Hg2+, the acetylcholine- or carbachol-activated sodium or chlo ride currents were increased to 300% and the effect was only partly re versible. The threshold concentration was 0.1 mu M Hg2+. 4. Contrary t o the effects on sodium and chloride currents, concentrations of 0.1-1 0 mu M Hg2+ caused a complete and irreversible blockade of K+-dependen t acetylcholine and carbachol currents. The block of the potassium cur rent was relatively fast and increased with time. The concentration of HgCl2 that gave a half-maximal blockade of the carbachol-activated po tassium current was 0.89 mu M. The chloride-dependent current elicited by glutamate on medial neurons was increased by HgCl2 as well. 5. The se results suggest that actions at agonist-activated channels must be considered as contributing to mercury neurotoxicity. It is possible th at the toxic actions of Hg2+ on synaptic transmission at both pre- and postsynaptic sites are important factors in the mechanism of Hg2+ tox icity.