BIPHASIC MODULATION OF THE STRYCHNINE-SENSITIVE GLYCINE RECEPTOR BY ZN2+

The effects of extracellular applications of Zn2+ ions on the strychni ne-sensitive glycine receptor were studied in cultured rat spinal cord neurons and with recombinant glycine receptors expressed in human emb ryonic kidney 293 cells. Nanomolar concentrations of Zn2+ enhanced the chloride ion current in response to brief applications of 100 mu M gl ycine. The enhancement of glycine responses increased from 20 nM to 1 mu M Zn2+. Higher concentrations of Zn2+ caused a reversal of the pote ntiation, followed by progressive inhibition of the glycine response u p to similar to 20-50 mu M Zn2+. The biphasic modulation by Zn2+ appea red essentially identical in native and recombinant glycine receptors. Biphasic Zn2+ modulation was observed both with picrotoxin-insensitiv e heteromeric (alpha 2/beta) receptors and with picrotoxin-sensitive h omomeric receptors consisting only of alpha 2 subunits. This suggests that the alpha subunit alone is sufficient for formation of two distin ct Zn2+ binding sites on the glycine receptor. The demonstration of Zn 2+ modulation of the strychnine-sensitive glycine receptor is of poten tial physiological importance, in view of the likely range of subsynap tic Zn2+ concentrations to which the receptor is exposed.