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Article
Nature Neuroscience  8, 736 - 744 (2005)
Published online: 15 May 2005; | doi:10.1038/nn1467

RNA editing produces glycine receptor alpha3P185L, resulting in high agonist potency

Jochen C Meier1, Christian Henneberger1, Igor Melnick1, 5, Claudia Racca2, Robert J Harvey3, Uwe Heinemann4, Volker Schmieden4 & Rosemarie Grantyn1

1  Department of Developmental Physiology, Johannes-Mueller Center of Physiology, Charité University Medicine, 10117 Berlin, Germany.

2  School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.

3  Department of Pharmacology, The School of Pharmacy, London WC1N 1AX, UK.

4  Department of Cellular Neurophysiology, Johannes-Mueller Center of Physiology, Charité University Medicine, 10117 Berlin, Germany.

5  Present address: Bogomoletz Institute of Physiology, Bogomoletz Str. 4, Kiev 01024, Ukraine.

Correspondence should be addressed to Jochen C Meier jochen.meier@charite.de
The function of supramedullary glycine receptors (GlyRs) is still unclear. Using Wistar rat collicular slices, we demonstrate GlyR-mediated inhibition of spike discharge elicited by low glycine (10 muM). Searching for the molecular basis of this phenomenon, we identified a new GlyR isoform. GlyRalpha3P185L, a result of cytidine 554 deamination, confers high glycine sensitivity (EC50 approx5 muM) to neurons and thereby promotes the generation of sustained chloride conductances associated with tonic inhibition. The level of GlyRalpha3-C554U RNA editing is sensitive to experimentally induced brain lesion, inhibition of cytidine deamination by zebularine and inhibition of mRNA transcription by actinomycin D, but not to blockade of protein synthesis by cycloheximide. Conditional regulation of GlyRalpha3P185L is thus likely to be part of a post-transcriptional adaptive mechanism in neurons with enhanced excitability.

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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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