Figure 2.

The intracellular Cl⁻ concentration determines the polarity of GABA response. The GABA action is excitatory in immature neurons because [Cl⁻]_i is high, owing to high levels of the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC1), which mediates inward transport of Cl⁻, and to low levels of the K⁺-Cl⁻ cotransporter (KCC2), which excludes Cl⁻ from the cell. In most neurons, the GABA response switches from excitation to inhibition during early postnatal development, due to the developmental decrease of the NKCC1 and increase of the KCC2. However, even in the mature neurons, neuronal damage down regulates the KCC2 and elevated Cl⁻ concentration shifts GABA response from hyperpolarization to depolarization, occasionally excitation. Most GnRH neurons show the unusual characteristic of being excited by GABA in the adult brain.