Fe 2+ decreases the taurine-induced Cl − current in acutely dissociated rat hippocampal neurons

Abstract

The effects of ferrous ions (Fe 2+) 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, Fe 2+ effectively depressed I tau in a concentration-dependent manner, with an IC 50 of 3.76 mM and Hill coefficient of 1.01, while preincubation with 1 mM Fe 2+ alone did not affect the following membrane currents elicited by taurine. The result suggests that resting taurine-gated channels are insensitive to Fe 2+. Since internal cell dialysis with 3 mM Fe 2+ failed to modify I tau, it was deduced that the site of action of Fe 2+ 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 Fe 2+ may act on the glycine receptor–chloride ionophore complex at a site distinct from where taurine binds. Various concentrations of Fe 2+ ranging from 0.1 to 20 mM depressed I tau and this extracellular depression was independent of membrane voltage. These results indicate that Fe 2+ decreases I tau in acutely dissociated rat hippocampal neurons and the inhibition of glycine receptors by Fe 2+ might be one possible approach through which Fe 2+ induces seizures.