Layer-specific expression of Cl− transporters and differential [Cl−]i in newborn rat cortex

GABA is the main inhibitory neurotransmitter in the adult brain. However, GABAergic transmission is depolarizing during early postnatal development, suggesting that changes in the expression of cation–Cl co-transporters regulating neuronal Cl homeostasis underlie the ontogeny of GABAergic functions. The developmental changes in the expressions of Cl co-transporter mRNAs in the neocortex were in opposite directions for NKCC1 (Cl uptake) and KCC2 (Cl extrusion). In the newborn, NKCC1 mRNA expression was highest in ventricular zone followed by cortical plate, and then by Layer V/VI, while the reverse was true for KCC2 mRNA. The [Cl]i levels were in the same rank order as for NKCC1 mRNA. Thus, the ontogeny of Cl homeostasis in neocortical neurons could be regulated via the differential expression of NKCC1 and KCC2.