Vale Carmen, Caminos Elena, Martinez-Galán Juan R, Juiz José M
School of Medicine and Centro Regional de Investigación Biomédica, Universidad de Castilla-La Mancha, Campus de Albacete, 02005 Albacete, Spain.
Hear Res. 2005 Aug;206(1-2):107-15. doi: 10.1016/j.heares.2005.03.012.
KCC2 is a neuron-specific Cl- transporter whose role in adult central neurons is to maintain low intracellular Cl- concentrations and, therefore, generate an inward-directed electrochemical gradient for Cl- needed for the hyperpolarizing responses to the inhibitory amino acids GABA and glycine. We report that the KCC2 protein is intensely expressed in CN neurons and preferentially associated with plasma membrane domains, consistent with GABA and glycinergic-mediated inhibition in this auditory nucleus. Postnatal KCC2 expression and distribution patterns are similar in developing and adult CN neurons and do not match the time course of GABergic or glycinergic synaptogenesis. Therefore, in the CN, neither KCC2 protein upregulation nor progressive integration in the plasma membrane seem to be involved in KCC2 developmental regulation. Considering that GABA and glycine are depolarizing during early postnatal development, it is conceivable that KCC2 is in place but inactive during early postnatal development in the CN and becomes active as inhibitory synaptogenesis proceeds. This notion is supported by the finding that the phosphorylation state of KCC2 differs from developing to adult CN, with the phosphorylated form predominating in the latter.
KCC2是一种神经元特异性氯离子转运体，其在成体中枢神经元中的作用是维持细胞内低氯离子浓度，从而为对抑制性氨基酸γ-氨基丁酸（GABA）和甘氨酸的超极化反应所需的氯离子产生内向电化学梯度。我们报道，KCC2蛋白在耳蜗核（CN）神经元中强烈表达，并优先与质膜结构域相关联，这与该听觉核中GABA和甘氨酸能介导的抑制作用一致。出生后KCC2在发育中的和成年CN神经元中的表达及分布模式相似，且与GABA能或甘氨酸能突触发生的时间进程不匹配。因此，在CN中，KCC2蛋白上调或在质膜中的逐步整合似乎均不参与KCC2的发育调控。鉴于在出生后早期发育过程中GABA和甘氨酸是去极化的，可以推测KCC2在CN出生后早期发育过程中已存在但无活性，并且随着抑制性突触发生的进行而变得活跃。这一观点得到以下发现的支持：KCC2的磷酸化状态在发育中的和成年的CN中有所不同，磷酸化形式在后者中占主导。
