Fig. 1.

The GABA switch. When the Gamma-aminobutyric acid (GABA) binds to the GABA_A receptor, which is a chloride channel, it opens the GABA_A receptor. When the intracellular chloride ion concentration is high because of the low expression of K⁺-Cl^- co-transporter 2 (KCC2), i.e., when the brain is immature, GABA makes chloride ions flow out from the cells, resulting in cell excitability (the membrane potential depolarizes). On the other hand, during normal brain development, KCC2 is up-regulated and Na⁺-K⁺-2Cl^- co-transporter 1 (NKCC1) is down-regulated. Therefore, in mature brains with lowered intracellular chloride ions, chloride ions flow into the cells when GABA functions. As a result, cells respond in an inhibitory manner (the membrane potential hyperpolarizes). The excitatory-to-inhibitory functional switch of GABA is referred to as the GABA switch.