Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (INCIA), Univ. Bordeaux, UMR 5287, CNRS, Bordeaux, France.
Adv Neurobiol. 2022;28:45-61. doi: 10.1007/978-3-031-07167-6_2.
Maturation of GABA/Glycine chloride-mediated synaptic inhibitions is crucial for the establishment of a balance between excitation and inhibition. GABA and glycine are excitatory neurotransmitters on immature neurons that exhibit elevated [Cl]. Later in development [Cl] drops leading to the occurrence of inhibitory synaptic activity. This ontogenic change is closely correlated to a differential expression of two cation-chloride cotransporters that are the Cl channel K/Cl co-transporter type 2 (KCC2) that extrudes Cl ions and the Na-K-2Cl cotransporter NKCC1 that accumulates Cl ions. The classical scheme built from studies performed on cortical and hippocampal networks proposes that immature neurons display high [Cl] because NKCC1 is overexpressed compared to KCC2 and that the co-transporters ratio reverses in mature neurons, lowering [Cl]. In this chapter, we will see that this classical scheme is not true in motoneurons (MNs) and that an early alteration of the chloride homeostasis may be involved in pathological conditions.
GABA/甘氨酸氯离子介导的突触抑制的成熟对于兴奋性和抑制性之间的平衡的建立至关重要。GABA 和甘氨酸是未成熟神经元上的兴奋性神经递质，表现出升高的氯离子浓度。在发育后期，氯离子浓度下降，导致抑制性突触活动的发生。这种个体发育变化与两种阳离子-氯离子共转运体的差异表达密切相关，这两种共转运体是氯离子通道 K/Cl 共转运体 2 (KCC2)，它将氯离子排出细胞外，而 Na-K-2Cl 共转运体 NKCC1 则将氯离子积累在细胞内。基于在皮质和海马网络上进行的研究建立的经典模型提出，未成熟神经元显示出高氯离子浓度，是因为与 KCC2 相比，NKCC1 过度表达，并且在成熟神经元中，共转运体的比例发生逆转，降低了氯离子浓度。在本章中，我们将看到，这个经典模型在运动神经元 (MNs)中并不适用，氯离子动态平衡的早期改变可能与病理条件有关。
