The role and the mechanism of γ-aminobutyric acid during central nervous system development

Abstract

γ-aminobutyric acid (GABA) is an inhibitory neurotransmitter in adult mammalian central nervous system (CNS). During CNS development, the role of GABA is switched from an excitatory transmitter to an inhibitory transmitter, which is caused by an inhibition of calcium influx into postsynaptic neuron derived from release of GABA. The switch is influenced by the neuronal chloride concentration. When the neuronal chloride concentration is at a high level, GABA acts as an excitatory neurotransmitter. When neuronal chloride concentration decreases to some degree, GABA acts as an inhibitory neurotransmitter. The neuronal chloride concentration is increased by Na⁺-K⁺-Cl⁻-Cl⁻ cotransporters 1 (NKCC1), and decreased by K⁺-Cl⁻ cotransporter 2 (KCC2).

摘要

γ-氨基丁酸 (γ-Aminobutyric acid, GABA) 是成年哺乳动物中枢神经系统内的抑制性神经递质。在中枢神经系统发育过程中, GABA由兴奋性神经递质转变为抑制性神经递质。其转变过程主要表现为GABA的释放由促进突触后神经元的Ca²⁺内流变为抑制突触后神经元的Ca²⁺内流。中枢神经元内GABA作用的转变受细胞内Cl⁻浓度的影响: 当细胞内Cl⁻浓度处于高水平时GABA发挥兴奋性神经递质的作用, 当细胞内Cl⁻浓度降低到一定程度后GABA发挥抑制性神经递质的作用。升高中枢神经元内Cl⁻ 浓度的是Na⁺-K⁺-Cl⁻-Cl⁻ 同向转运蛋白1 (Na⁺-K⁺-Cl⁻-Clcotransporters1, NKCC1), 而K⁺-Cl⁻协同转运蛋白2 (K⁺-Cl⁻ cotransporter 2, KCC2) 则使中枢神经元内Cl⁻浓度降低。