Fe²⁺ decreases the taurine-induced Cl^- current in acutely dissociated rat hippocampal neurons

The effects of ferrous ions (Fe²⁺) on taurine-induced Cl^- current (I_tau) recorded from single neurons, which was freshly isolated from the rat hippocampal CA1 area, were studied with conventional whole-cell recording under voltage-clamp conditions. Using standard pharmacological approaches, we found that the currents gated by concentrations of taurine (≤10 mM), which existed in about 90% of the hippocampal neurons tested, were predominantly mediated by strychnine-sensitive glycine receptors. When co-applied with taurine, Fe²⁺ effectively depressed I_tau in a concentration-dependent manner, with an IC₅₀ of 3.76 mM and Hill coefficient of 1.01, while preincubation with 1 mM Fe²⁺ alone did not affect the following membrane currents elicited by taurine. The result suggests that resting taurine-gated channels are insensitive to Fe²⁺. Since internal cell dialysis with 3 mM Fe²⁺ failed to modify I_tau, it was deduced that the site of action of Fe²⁺ is extracellular. Furthermore, the Lineweaver-Burke double reciprocal plot of normalized response to taurine against the concentration of taurine illustrated that the depression of I_tau was noncompetitive, therefore Fe²⁺ may act on the glycine receptor-chloride ionophore complex at a site distinct from where taurine binds. Various concentrations of Fe²⁺ ranging from 0.1 to 20 mM depressed I_tau and this extracellular depression was independent of membrane voltage. These results indicate that Fe²⁺ decreases I_tau in acutely dissociated rat hippocampal neurons and the inhibition of glycine receptors by Fe²⁺ might be one possible approach through which Fe²⁺ induces seizures.