Mercuric ions are potent noncompetitive antagonists of human brain kainate receptors expressed in Xenopus oocytes.

Kainate receptors are one of the major subtypes of excitatory amino acid receptors in the vertebrate central nervous system. Using Xenopus oocytes injected with RNA from human temporal cortex, it is possible to detect electrophysiologically the expression of this receptor subtype in these cells. Ions of the group IIb elements, particularly mercuric ions, are highly potent, noncompetitive inhibitors of these human brain kainate receptors. Mercury-containing sulfhydryl reagents are also very effective, irreversible blockers of the kainate-gated currents of these oocytes. The recovery of kainate-activated currents after washout of Hg2+ is slow and incomplete relative to that seen after treatment either with Cd2+ or Zn2+. Cysteine or dithiothreitol can accelerate this recovery of kainate-inducible currents after Hg2+ inhibition. Besides the toxicological implications of these results, mercury compounds may be useful for future studies of the structure and physiology of the kainate receptor-channel complex.