Copper Ions Reduce the Effect of Protons on Desensitization of Glycine Receptors

Chloride current (I-Gly) evoked by the rapid (600 msec) application of glycine on isolated pyramidal neurons of the rat hippocampus was recorded using the patch clamp technique. We studied the effect of individual or combined application of copper ions (Cu2+) and protons (H+) on I-Gly. It was found that both Cu2+ (10 mu M) and H+ (pH 7.0 and 6.0) applied separately caused a fast and reversible effect on I-Gly that included two components: a decrease in peak amplitude (I-peak) and a decrease in the desensitization time constant (tau(des)). During combined application, the effects on I-peak were additive, which indicates the independence of the mechanisms of these effects. At the same time, the effect of combined application of Cu2+ and H+ on tau(des) was not additive and sometimes a slowdown of the total desensitization was observed. The latter result suggests that H+ and Cu2+ can play the role of mutual antagonists when they affect the desensitization of GlyR.