Delpy Alain, Allain Anne-Emilie, Meyrand Pierre, Branchereau Pascal
Centre de Neuroscience Intégratives et Cognitives, Université Bordeaux and CNRS, UMR 5228, Avenue des Facultés, 33405 Talence cedex, France.
J Physiol. 2008 Feb 15;586(4):1059-75. doi: 10.1113/jphysiol.2007.146993. Epub 2007 Dec 20.
Early in development, GABA and glycine exert excitatory action that turns to inhibition due to modification of the chloride equilibrium potential (E(Cl)) controlled by the KCC2 and NKCC1 transporters. This switch is thought to be due to a late expression of KCC2 associated with a NKCC1 down-regulation. Here, we show in mouse embryonic spinal cord that both KCC2 and NKCC1 are expressed and functional early in development (E11.5-E13.5) when GABA(A) receptor activation induces strong excitatory action. After E15.5, a switch occurs rendering GABA unable to provide excitation. At these subsequent stages, NKCC1 becomes both inactive and less abundant in motoneurons while KCC2 remains functional and hyperpolarizes E(Cl). In conclusion, in contrast to other systems, the cotransporters are concomitantly expressed early in the development of the mouse spinal cord. Moreover, whereas NKCC1 follows a classical functional extinction, KCC2 is highly expressed throughout both early and late embryonic life.
在发育早期，γ-氨基丁酸（GABA）和甘氨酸发挥兴奋性作用，由于由KCC2和NKCC1转运体控制的氯离子平衡电位（E(Cl)）发生改变，这种作用转变为抑制作用。这种转换被认为是由于KCC2的晚期表达与NKCC1的下调相关。在此，我们在小鼠胚胎脊髓中发现，在发育早期（E11.5-E13.5），当GABA(A)受体激活诱导强烈的兴奋性作用时，KCC2和NKCC1均有表达且发挥功能。在E15.5之后，发生转换，使得GABA无法提供兴奋作用。在随后这些阶段，NKCC1在运动神经元中变得既无活性且丰度降低，而KCC2仍发挥功能并使E(Cl)超极化。总之，与其他系统不同，共转运体在小鼠脊髓发育早期同时表达。此外，虽然NKCC1遵循经典的功能消失模式，但KCC2在胚胎早期和晚期均高度表达。
