Distinct regulation of β2 and β3 subunit-containing cerebellar synaptic GABAa receptors by calcium/calmodulin-dependent protein kinase II

Abstract

Modulation of GABAA 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 α-calcium/calmodulin-dependent protein kinase II (α-CaMK-II) in cerebellar granule neurons differentially affects populations of IPSCs that correspond to GABAA receptors containing different subtypes of β subunit. By using transgenic mice, we ascertained that α-CaMK-II increased IPSC amplitude but not the decay time by acting via β2 subunit-containing GABAA receptors. In contrast, IPSC populations whose decay times were increased by α-CaMK-II were most likely mediated by β3 subunit-containing receptors. Expressing α-CaMK-II with mutations that affected kinase function revealed that Ca2+ and calmodulin binding is crucial for α-CaMK-II modulation of GABAA receptors, whereas kinase autophosphorylation is not. These findings have significant consequences for understanding the role of synaptic GABAA receptor heterogeneity within neurons and the precise regulation of inhibitory transmission by CaMK-II phosphorylation. Copyright © 2008 Society for Neuroscience.