The effects of Zn
2+ on the glycine receptor channels expressed in rat cultured neurons and
Xenopus oocytes injected with complementary RNA encoding the adult form of glycine receptor subunit (α1) were examined. Application of glycine at 100μ M caused generation of inward currents when the neurons were voltage-clamped a-60mV. In the presence of Zn
2+ at 1μM, the glycine-induced currents increased currents by up to 2-fold compared with the control responses. The augmented responses were reversed within 2 minutes after washing out Zn
2+. Zn
2+ alone did not cause any change in membrane currents. In the experiments with oocytes expressing α1 homomeric glycine receptors, Zn
2+ (0.1-10μM) enhanced the glycine-induced currents by up to 2 to 5-fold compared with the control responses in a reversible manner. Other divalent cations such as Cd
2+, Ni
2+, Co
2+, Mn
2+, Mg
2+ and Cu
2+ at low concentrations (1-10μM) had no effect on the glycine currents. Experiments using a combined application of Zn
2+ with glycine revealed that the action site of Zn
2+ is on extracellular space. These results suggest that Zn
2+ binds to a specific site on the α subunit of the glycine receptor to positively regulate the channel activity.
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