The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation
The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation
复制标题
作者：
Rivera, C;Voipio, J;Kaila, K
GABA（γ-氨基丁酸）是成人大脑中主要的抑制性递质，它通过激活阴离子（主要是 Cl-）渗透性 GABA(A) 受体发挥其快速超极化作用(1)。然而，在早期神经元发育过程中，GABA(A) 受体介导的反应通常是去极化的(2,3)，这可能是控制多种 Ca2+ 依赖性发育现象（包括神经元）的关键因素。增殖、迁移和靶向(4-6)。然而，迄今为止，神经元电生理表型这种转变的分子机制尚不清楚。在这里，我们发现，在大鼠海马的锥体神经元中，GABA（A）介导的从去极化到超极化反应的个体发生变化与神经元 Cl- 挤出 K+/Cl- 协同转运蛋白 KCC2 表达的发育诱导相结合（参考文献 7）。 KCC2 表达的反义寡核苷酸抑制会导致 GABA 逆转电位显着正向变化，这是功能成熟的海马锥体神经元的反应。这些数据支持这样的结论：KCC2是促进大脑中快速超极化突触后抑制的主要Cl-挤出机。
GABA (gamma-aminobutyric acid) is the main inhibitory transmitter in the adult brain, and it exerts its fast hyperpolarizing effect through activation of anion (predominantly Cl-)-permeant GABA(A) receptors(1), However, during early neuronal development, GABA(A)-receptor-mediated responses are often depolarizing(2,3), which may be a key factor in the control of several Ca2+-dependent developmental phenomena, including neuronal proliferation, migration and targeting(4-6). To date, however, the molecular mechanism underlying this shift in neuronal electrophysiological phenotype is unknown. Here we show that, in pyramidal neurons of the rat hippocampus, the ontogenetic change in GABA(A)-mediated responses from depolarizing to hyperpolarizing is coupled to a developmental induction of the expression of the neuronal Cl--extruding K+/Cl- co-transporter, KCC2 (ref. 7). Antisense oligonucleotide inhibition of KCC2 expression produces a marked positive shift in the reversal potential of GABA, responses in functionally mature hippocampal pyramidal neurons. These data support the conclusion that KCC2 is the main Cl- extruder to promote fast hyperpolarizing postsynaptic inhibition in the brain.