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1 Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama, USA
* To whom correspondence should be addressed. E-mail: Mcmahon{at}physiology.uab.edu.
Previously we have shown that strychnine-sensitive glycine-gated chloride channels (GlyRs) are functionally expressed by CA1 pyramidal cells and GABAergic interneurons in mature rat hippocampal slices. We now report that glycine application to dentate granule cells and hilar interneurons recorded in acute slices from adolescent rats elicits a strychnine-sensitive current similar to glycine-mediated currents recorded in area CA1, indicating that GlyRs are also present on neurons in the dentate gyrus. This finding suggests that GlyRs have a widespread distribution in the hippocampal region. The physiological role of GlyRs in forebrain is unclear, but it is possible that these receptors mediate neuronal inhibition, like GABAA receptors, and thus could be a novel target for antiepileptic therapy. Therefore, we tested the hypothesis that activation of inhibitory GlyRs could suppress neuronal hyperexcitability in dentate, a brain region vulnerable to epileptic activity. In whole-cell current clamp recordings of granule cells, we observed a membrane potential hyperpolarization followed by cessation of the action potential firing pattern in hyperexcitable slices induced by elevated extracellular K+ or by blocking GABAA receptors with bicuculline. The GlyR antagonist, strychnine, prevented the anti-epileptic effect of glycine. These results demonstrate that glycine acting at GlyRs elicits neuronal inhibition in dentate. Further, our findings suggest the possibility that these receptors could be a therapeutic target for the treatment of epilepsy.
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