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The Journal of Neuroscience, July 23, 2008, 28(30):7574-7584; doi:10.1523/JNEUROSCI.5531-07.2008

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Cellular/Molecular
Distinct Regulation of β2 and β3 Subunit-Containing Cerebellar Synaptic GABA_A Receptors by Calcium/Calmodulin-Dependent Protein Kinase II

Catriona M. Houston, Alastair M. Hosie, and Trevor G. Smart

Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom

Correspondence should be addressed to Prof. Trevor G. Smart, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: t.smart{at}ucl.ac.uk

Modulation of GABA_A receptor function and inhibitory synaptic transmission by phosphorylation has profound consequences for the control of synaptic plasticity and network excitability. We have established that activating -calcium/calmodulin-dependent protein kinase II (-CaMK-II) in cerebellar granule neurons differentially affects populations of IPSCs that correspond to GABA_A receptors containing different subtypes of β subunit. By using transgenic mice, we ascertained that -CaMK-II increased IPSC amplitude but not the decay time by acting via β2 subunit-containing GABA_A receptors. In contrast, IPSC populations whose decay times were increased by -CaMK-II were most likely mediated by β3 subunit-containing receptors. Expressing -CaMK-II with mutations that affected kinase function revealed that Ca²⁺ and calmodulin binding is crucial for -CaMK-II modulation of GABA_A receptors, whereas kinase autophosphorylation is not. These findings have significant consequences for understanding the role of synaptic GABA_A receptor heterogeneity within neurons and the precise regulation of inhibitory transmission by CaMK-II phosphorylation.

Key words: GABA_A receptor; CaMK-II; β2 subunit; β3 subunit; synaptic inhibition; phosphorylation

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Received Dec. 14, 2007; revised April 22, 2008; accepted June 5, 2008.

Correspondence should be addressed to Prof. Trevor G. Smart, Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Email: t.smart{at}ucl.ac.uk

This article has been cited by other articles:

				C. M. Houston, D. P. Bright, L. G. Sivilotti, M. Beato, and T. G. Smart Intracellular Chloride Ions Regulate the Time Course of GABA-Mediated Inhibitory Synaptic Transmission J. Neurosci., August 19, 2009; 29(33): 10416 - 10423. [Abstract] [Full Text] [PDF]

				C. M. Houston, Q. He, and T. G. Smart CaMKII phosphorylation of the GABAA receptor: receptor subtype- and synapse-specific modulation J. Physiol., May 15, 2009; 587(10): 2115 - 2125. [Abstract] [Full Text] [PDF]

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