Tonic activation of group I mGluRs modulates inhibitory synaptic strength by regulating KCC2 activity
Tonic activation of group I mGluRs modulates inhibitory synaptic strength by regulating KCC2 activity
复制标题
DOI：
10.1113/jphysiol.2008.157024
复制
发表时间：
2008-10-15
影响因子：
5.5
通讯作者：
Gegelashvili, Georgi
中科院分区：
文献类型：
--
作者：
Banke, Tue G.;Gegelashvili, Georgi
速尿敏感性钾-氯共转运蛋白（KCC 2）在中枢神经系统内许多神经元中建立细胞内氯浓度方面起重要作用。因此，KCC 2功能的调节将调节突触GABA能输入的逆转电位，从而设定抑制性传递的强度。我们发现，紧张性激活组I代谢型谷氨酸受体（mGluR 1 s）调节抑制性突触强度通过调制KCC 2功能在海马CA 3区的锥体神经元。具体而言，I组mGluRs通过激活蛋白激酶C依赖性途径来改变KCC 2活性，从而改变细胞内氯离子浓度，并因此抑制突触输入。谷氨酸能和氯离子转运系统之间的这种相互作用突出了一种新的稳态机制，即环境谷氨酸水平通过设置KCC 2的活性水平直接调节抑制性突触张力。因此，mGluRs准备发挥关键作用，在海马体中的兴奋和抑制系统之间提供直接的相互作用。
The furosemide-sensitive potassium-chloride cotransporter (KCC2) plays an important role in establishing the intracellular chloride concentration in many neurons within the central nervous system. Consequently, modulation of KCC2 function will regulate the reversal potential for synaptic GABAergic inputs, thus setting the strength of inhibitory transmission. We show that tonic activation of group I metabotropic glutamate receptors (mGluR1s) regulates inhibitory synaptic strength via modulation of KCC2 function in pyramidal neurons of the hippocampal CA3 area. Specifically, group I mGluRs signal via activation of a protein kinase C-dependent pathway to alter KCC2 activity, thereby altering the intracellular chloride concentration, and thus inhibitory synaptic input. This interaction between the glutamatergic and chloride transport systems highlights a novel homeostatic mechanism whereby ambient glutamate levels directly regulate the inhibitory synaptic tone by setting the activity level of KCC2. Thus, mGluRs are poised to play a pivotal role in providing a direct interplay between the excitatory and inhibitory systems in the hippocampus.