Distinct Regulation of 2 and 3 Subunit-Containing Cerebellar Synaptic GABAA Receptors by Calcium/Calmodulin-Dependent Protein Kinase II

C. M. Houston, A. M. Hosie, T. G. Smart
2008 Journal of Neuroscience  
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 ␤ subunit. By using transgenic mice, we ascertained that ␣-CaMK-II
more » ... at ␣-CaMK-II increased IPSC amplitude but not the decay time by acting via ␤2 subunit-containing GABA A receptors. In contrast, IPSC populations whose decay times were increased by ␣-CaMK-II were most likely mediated by ␤3 subunit-containing receptors. Expressing ␣-CaMK-II with mutations that affected kinase function revealed that Ca 2ϩ 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.
doi:10.1523/jneurosci.5531-07.2008 pmid:18650335 fatcat:afpaiporkncc3g4l2r7l2g52zm