Early expression of KCC2 in rat hippocampal cultures augments expression of functional GABA synapses
Early expression of KCC2 in rat hippocampal cultures augments expression of functional GABA synapses
复制标题
DOI：
10.1113/jphysiol.2005.089821
复制
发表时间：
2005-08-01
影响因子：
5.5
通讯作者：
Medina, I
中科院分区：
文献类型：
--
作者：
Chudotvorova, I;Ivanov, A;Medina, I
由于[Cl-]的减少，GABA能突触的发育与GABA作用的兴奋性到抑制性转变有关(i)。这是由于出生后K+- cl -共转运体KCC2的表达延迟，其在出生时水平较低，在出生后的前几周达到峰值。是否共转运蛋白的表达和兴奋性到抑制性的转变对GABA(A)受体和突触的运作有其他影响尚不清楚。我们已经在早期发育阶段的未成熟神经元中表达了KCC2，并确定了其对GABA和谷氨酸突触形成的影响。我们报道，早期表达的共转运体选择性地增强了GABA能突触：GABA受体和突触的密度显著增加，GABA能微型突触后电流的频率增加。谷氨酸突触的密度和AMPA微型突触后电流的频率不受影响。我们得出结论，KCC2的表达和[Cl-](i)的减少在GABA能网络的构建中起着关键作用，该网络的作用从兴奋转移到GABA的抑制转移。
The development of GABAergic synapses is associated with an excitatory to inhibitory shift of the actions of GABA because of a reduction of [Cl-](i). This is due to a delayed postnatal expression of the K+-Cl- cotransporter KCC2, which has low levels at birth and peaks during the first few postnatal weeks. Whether the expression of the cotransporter and the excitatory to inhibitory shift have other consequences on the operation of GABA(A) receptors and synapses is not yet known. We have now expressed KCC2 in immature neurones at an early developmental stage and determined the consequences on the formation of GABA and glutamate synapses. We report that early expression of the cotransporter selectively enhances GABAergic synapses: there is a significant increase of the density of GABA(A) receptors and synapses and an increase of the frequency of GABAergic miniature postsynaptic currents. The density of glutamate synapses and frequency of AMPA miniature postsynaptic currents are not affected. We conclude that the expression of KCC2 and the reduction of [Cl-](i) play a critical role in the construction of GABAergic networks that extends beyond the excitatory to inhibitory shift of the actions of GABA.