EXPRESSION OF THE NA-K-2CL COTRANSPORTER IS DEVELOPMENTALLY-REGULATEDIN POSTNATAL RAT BRAINS - A POSSIBLE MECHANISM UNDERLYING GABAS EXCITATORY ROLE IN IMMATURE BRAIN

An inhibitory neurotransmitter in mature brain, gamma-aminobutyric aci d (GABA) also appears to be excitatory early in development. The mecha nisms underlying this shift are not well understood. In vitro studies have suggested that Na-K-CI cotransport may have a role in modulating immature neuronal and oligodendrocyte responses to the neurotransmitte r GABA. An in vivo developmental study would test this view. Therefore , we examined the expression of the BSC2 isoform of the Na-K-2Cl cotra nsporter in the postnatal developing rat brain. A comparison of sectio ns from developing rat brains by in situ hybridization revealed a well -delineated temporal and spatial pattern of first increasing and then diminishing cotransporter expression. Na-K-2Cl mRNA expression in the cerebral cortex and hippocampus was highest in the first week of postn atal life and then diminished from postnatal day (PND) 14 to adult. Co transporter signal in white-matter tracts of the cerebrum, cerebellum, peaked at PND 14. Expression was detected in cerebellar progenitor ce lls of the external granular layer, in internal granular layer cells a t least as early as PND 7, and in Purkinje cells beginning at PND 14. Double-labeling immunofluorescence of brain sections with anti-BSC2 an tibody and cell type-specific antibodies confirmed expression of the c otransporter gene product in neurons and oligodendrocytes in the white matter in a pattern similar to that determined by lit situ hybridizat ion. The temporal pattern of expression of the Na-K-2Cl cotransporter in the postnatal rat brain supports the hypothesis that the cotranspor ter is the mechanism of intracellular Cl- accumulation in immature neu rons and oligodendrocytes. (C) 1997 John Wiley & Sons, Inc.