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: Kuai Yu, Shao-Yu Ge, Di-Yun Ruan
• Journal: Brain research (Brain Res) Vol. 960 Issue 1-2 Pg. 25-35 (Jan 17 2003) ISSN: 0006-8993 [Print] Netherlands
• PMID: 12505654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chloride Channels
• GABA Antagonists
• Glycine Agents
• Receptors, GABA
• Taurine
• Iron
• Strychnine
• Bicuculline

Topics

• Animals
• Bicuculline (pharmacology)
• Chloride Channels (drug effects)
• Electrophysiology
• GABA Antagonists (pharmacology)
• Glycine Agents (pharmacology)
• Hippocampus (cytology, drug effects, metabolism)
• In Vitro Techniques
• Ion Channel Gating (drug effects)
• Iron (pharmacology)
• Kinetics
• Membrane Potentials (drug effects)
• Neuroeffector Junction (drug effects)
• Neurons (drug effects, metabolism)
• Patch-Clamp Techniques
• Pyramidal Cells (drug effects, metabolism)
• Rats
• Rats, Wistar
• Receptors, GABA (drug effects)
• Strychnine (pharmacology)
• Taurine (antagonists & inhibitors, pharmacology)