Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+.
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.
Bloomenthal
A B
AB
Department of Anesthesia and Critical Care, University of Chicago, Illinois 60637.
Goldwater
E
E
Pritchett
D B
DB
Harrison
N L
NL
D000818:Animals; D002478:Cells, Cultured; D004357:Drug Synergism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018009:Receptors, Glycine / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
D018009:Receptors, Glycine; D013331:Strychnine; D015032:Zinc