Distinct regulation of β2 and β3 subunit-containing cerebellar synaptic GABAA receptors by calcium/calmodulin-dependent protein kinase II
Distinct regulation of β2 and β3 subunit-containing cerebellar synaptic GABAA receptors by calcium/calmodulin-dependent protein kinase II
复制标题
DOI：
10.1523/jneurosci.5531-07.2008
复制
发表时间：
2008-07-23
影响因子：
5.3
通讯作者：
Smart, Trevor G.
中科院分区：
文献类型：
--
作者：
Houston, Catriona M.;Hosie, Alastair M.;Smart, Trevor G.
通过磷酸化调节GABA(A)受体功能和抑制突触传递对突触可塑性和网络兴奋性的控制具有深远的影响。我们已经确定，激活小脑颗粒神经元中的α -钙/钙调素依赖性蛋白激酶II （α - camk -II）会对含有不同亚型β亚基的GABA(A)受体对应的IPSCs群体产生不同的影响。通过转基因小鼠，我们确定了α - camk - ii通过含有GABA(A)受体的β 2亚基作用增加IPSC振幅，但不增加衰减时间。相比之下，α - camk - ii增加衰变时间的IPSC群体很可能是由含有β 3亚基的受体介导的。表达影响激酶功能突变的α - camk - ii表明Ca2+和钙调蛋白结合对α - camk - ii调节GABA(A)受体至关重要，而激酶自磷酸化则不是。这些发现对于理解突触GABA(A)受体在神经元内异质性的作用以及CaMK-II磷酸化对抑制传递的精确调控具有重要意义。
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 alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMK-II) in cerebellar granule neurons differentially affects populations of IPSCs that correspond to GABA(A) receptors containing different subtypes of beta subunit. By using transgenic mice, we ascertained that alpha-CaMK-II increased IPSC amplitude but not the decay time by acting via beta 2 subunit-containing GABA(A) receptors. In contrast, IPSC populations whose decay times were increased by alpha-CaMK-II were most likely mediated by beta 3 subunit-containing receptors. Expressing alpha-CaMK-II with mutations that affected kinase function revealed that Ca2+ and calmodulin binding is crucial for alpha-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.