Zn2+ enhancement of the recombinant 5-HT3 receptor is modulated by divalent cations

The modulation by Zn2+ of recombinant murine 5-hydroxytryptamine(3A) (5-HT3A) receptor responses and its modification by Ca2+ or Mg2+ were studied using whole-cell voltage clamp and radioligand binding techniques. In the absence of other added divalent cations Zn2+ enhanced the response to 5-HT by increasing maximum peak current (I-max) to a maximum of 122.5%, decreasing the rate of desensitization (maximum t(1/2) = 210%), and decreasing the EC50 by approximately two fold. In the presence of Ca2+ or Mg2+, the effects of Zn2+ on I-max and t(1/2) were still manifest, although higher Zn2+ concentrations were required; however, the effect on EC50 was abolished. Zn2+ also enhanced [H-3]agonist but not [H-3]antagonist binding. We propose there is more than one Zn2+ binding site on the 5-HT3 receptor molecule, and that one or more of these sites may also bind Ca2+ and Mg2+. (C) 2000 Elsevier Science B.V. All rights reserved.