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This Article Full Text Full Text (PDF) All Versions of this Article: 98/6/3666    most recent 00500.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhang, H. X. Articles by Thio, L. L. Search for Related Content PubMed PubMed Citation Articles by Zhang, H. X. Articles by Thio, L. L.

Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

¹Departments of Neurology, ²Pediatrics, and ³Anatomy and Neurobiology, ⁴Division of Pediatrics and Developmental Neurology, ⁵Hope Center for Neurological Disorders, and ⁶Pediatric Epilepsy Center, Washington University School of Medicine, St. Louis, Missouri

Submitted 3 May 2007; accepted in final form 28 September 2007

Although extracellular Zn²⁺ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn²⁺ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn²⁺ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 µM Zn²⁺, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 µM glycine (EC₂₅) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 µM Zn²⁺. At least part of this effect resulted from Zn²⁺ enhancing the GlyR-induced decrease in input resistance. Sustained 20 µM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg²⁺. However, sustained 20 µM glycine applications depressed neuronal bursting in 1 µM Zn²⁺. Zn²⁺ did not enhance the inhibitory effects of sustained 60 µM glycine (EC₇₀) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn²⁺ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn²⁺ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.