title: Fe2+ 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 (<or=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.
authors.affiliation: School of Life Science, University of Science and Technology of China, Hefei Anhui, 230027 PR China.
authors.forename: Kuai
authors.initials: K
authors.lastname: Yu
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Ge
authors.forename: Di-Yun
authors.initials: DY
authors.lastname: Ruan
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects*; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009451:Neuroeffector Junction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects; D013331:Strychnine / Q000494:pharmacology; D013654:Taurine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; D018756:GABA Antagonists; D018684:Glycine Agents; D018079:Receptors, GABA; D013654:Taurine; D007501:Iron; D013331:Strychnine; D001640:Bicuculline