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Glycine receptor subunit composition alters the action of GABA antagonists

Published online by Cambridge University Press:  23 July 2007

PING LI  and
MALCOLM SLAUGHTER
PING LI
Affiliation:
Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York Current address: Washington University School of Medicine, Department of Anesthesiology, Campus Box 8054, 660 S. Euclid Avenue, St. Louis, MO 63110.
MALCOLM SLAUGHTER
Affiliation:
Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York
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Abstract

GABA receptor antagonists produce an unexpectedly significant inhibition of native glycine receptors in retina and in α1 or α2 homomeric glycine receptors (GlyRs) expressed in HEK 293 cells. In this study we evaluate this phenomenon in heteromeric glycine receptors, formed by mixing α1, α2, and β subunits. Picrotoxinin, picrotin, SR95531, and bicuculline are all more effective antagonists at GlyRs containing α2 subunits than α1 subunits. Inclusion of β subunits reduces the inhibitory potency of picrotoxinin and picrotin but increases the potency of SR95531 and bicuculline. As a result of these two factors, bicuculline is particularly poor at discriminating GABA and glycine receptors. Picrotin, which has been reported to be inactive at GABA receptors, blocks glycine currents in retina and in HEK293 cells, suggesting its utility as a selective glycine antagonist. However, picrotin is a more potent inhibitor of GABA than glycine in retinal neurons. We also tested if GABA and glycine receptor subunits can combine to form functional receptors. If GABAAR γ2S subunits are co-expressed with GlyR α subunits, the mixed receptor is glycine-sensitive and GABA-insensitive. But the mixed receptor exhibits a non-competitive picrotoxinin inhibition that is not observed in the homomeric GlyRs. This suggests that glycine and GABA subunits can co-assemble to form functional glycine receptors.

Keywords

BicucullinePicrotinSR95531PicrotoxininRetina
Type
Research Article
Information
Visual Neuroscience , Volume 24 , Issue 4 , July 2007 , pp. 513 - 521
Copyright
© 2007 Cambridge University Press

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