RT Journal Article SR Electronic T1 Copper Block of Extrasynaptic GABAA Receptors in the Mature Cerebellum and Striatum JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 13431 OP 13435 DO 10.1523/JNEUROSCI.1908-13.2013 VO 33 IS 33 A1 Thomas P. McGee A1 Catriona M. Houston A1 Stephen G. Brickley YR 2013 UL http://www.jneurosci.org/content/33/33/13431.abstract AB Inhibition of GABAA receptors by Cu2+ has been appreciated for some time, but differences between synaptic and extrasynaptic GABAA receptors have not been explored. We show that Cu2+ potently blocks steady-state GABA currents mediated by extrasynaptic δ subunit-containing GABAA receptors (δ-GABAARs) with an IC50 of 65 nm. This compares with an IC50 of 85 μm for synaptic γ subunit-containing GABAARs (γ-GABAARs). To test the significance of this subunit selectivity, we examined the blocking action of Cu2+ on neurons of the mouse cerebellum and striatum, brain regions that are known to express both types of receptor. Cu2+ was shown to significantly reduce tonic inhibition mediated by extrasynaptic δ-GABAARs with little action on phasic inhibition mediated by conventional synaptic γ-GABAARs. We speculate on the implications of these observations for conditions, such as Wilson's disease, that can involve raised Cu2+ levels in the brain.