Figure 2.

GABA_A signalling shifts from depolarizing to hyperpolarising responses are mediated by developmental expression of KCC2 and NKCC1 in the brain (neocortical neurons) of rats. The differential expression of these channels regulates intracellular Cl⁻ concentration ([Cl⁻]_i) and therefore determines the activity of γ-aminobutyric acid (GABA). Na⁺–K⁺–Cl⁻ cotransporter 1 (NKCC1) pumps Cl⁻ into neurons; its expression is high in the early postnatal period, decreasing as maturation proceeds. The expression pattern for K⁺–2Cl⁻ cotransporter 2 (KCC2), responsible for Cl⁻ efflux, is directly opposite. In the embryonic and early postnatal periods, [Cl⁻]_i is high, and so GABAergic signalling is excitatory (depolarising); as maturation occurs, [Cl⁻]_i decreases, initiating the development hyperpolarising shift, whereby GABAergic signalling becomes inhibitory. Figure elements were taken and modified from Tillman and Zhang [63].