Fe2+ and Fe3+ in micromolar concentrations modulate glycine-induced Cl- current in rat hippocampal neurons

The effects of Fe2+ and Fe3+ on glycine-activated chloride current (I-Gly were studied in rat isolated pyramidal hippocampal neurons using patch-clamp technique in whole-cell configuration. 25,100 or 500 mu M glycine was applied for 600 ms with 40s intervals. Fe2+ and Fe3+ were co-applied with glycine in the range of concentrations of 0.01-100 mu M. We found that Fe2+ and Fe3+ affected I-Gly in a similar manner. Two types of effects of iron on I-Gly were observed. In low concentrations (0.1 mu M) Fe ions caused an acceleration of the lay desensitization, and the effect was more pronounced for I-Gly induced by 100 and 500 mu M glycine than by 25 mu M glycine. Higher Fe concentrations (1-100 mu M) decreased the peak amplitude of I-Gly with weak influence on its kinetics. The values of IC50 of the effect were close to 10 mu M for all glycine concentrations tested. The effect of iron on I-Gly peak did not depend on the membrane potential. This inhibition was noncompetitive and voltage-independent, suggesting that Fe ions do not exert their action on the agonist binding site of GlyRs or block the channel pore. An important characteristic of both effects of Fe was their progressive development during repetitive Fe applications (use-dependence). Our results suggest an existence of at least two binding sites for Fe ions which vary in affinity and mechanism of action, with the low-affinity site suppressing the activity of the high-affinity one. Physiological implication of our observations is that Fe ions in low micromolar concentrations can suppress tonic inhibition and cause hyperexcitability in hippocampus. (C) 2015 Elsevier Inc. All rights reserved.