TY - JOUR T1 - Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1156 LP - 1159 VL - 46 IS - 6 AU - A B Bloomenthal AU - E Goldwater AU - D B Pritchett AU - N L Harrison Y1 - 1994/12/01 UR - http://molpharm.aspetjournals.org/content/46/6/1156.abstract N2 - The effects of extracellular applications of Zn2+ ions on the strychnine-sensitive glycine receptor were studied in cultured rat spinal cord neurons and with recombinant glycine receptors expressed in human embryonic kidney 293 cells. Nanomolar concentrations of Zn2+ enhanced the chloride ion current in response to brief applications of 100 microM glycine. The enhancement of glycine responses increased from 20 nM to 1 microM Zn2+. Higher concentrations of Zn2+ caused a reversal of the potentiation, followed by progressive inhibition of the glycine response up to approximately 20-50 microM Zn2+. The biphasic modulation by Zn2+ appeared essentially identical in native and recombinant glycine receptors. Biphasic Zn2+ modulation was observed both with picrotoxin-insensitive heteromeric (alpha 2/beta) receptors and with picrotoxin-sensitive homomeric receptors consisting only of alpha 2 subunits. This suggests that the alpha subunit alone is sufficient for formation of two distinct Zn2+ binding sites on the glycine receptor. The demonstration of Zn2+ modulation of the strychnine-sensitive glycine receptor is of potential physiological importance, in view of the likely range of subsynaptic Zn2+ concentrations to which the receptor is exposed. ER -