Cl⁻ uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1

Abstract

GABA is the principal inhibitory neurotransmitter inand NKCC1 mRNA expression were each higher in cortical plate (CP) neurones than in the presumably older layer V/VI pyramidal neurones in a given slice. The pharmacological effects of bumetanide on E GABA were consistent with the different expression levels of NKCC1 mRNA. These data suggest that NKCC1 may play a pivotal role in the generation of GABA-mediated depolarization in immature CP cells, while KCC2 promotes the later maturation of GABAergic inhibition in the rat neocortex.

Imaging synaptic inhibition in transgenic mice expressing the chloride indicator, Clomeleon

“…Both the time course and the magnitude of the developmental decreases in [Cl − ] i reported by Clomeleon are consistent with previous estimates based on electrophysiological measurements (Owens et al, 1996) and the expression profiles of NKCC1 and KCC2 (Rivera et al, 1999;Stein et al, 2004;Yamada et al, 2004;Rivera et al, 2005). Some of these studies showed a rather large variability, both within a given preparation as well as among different cell types, consistent with our finding of a wide distribution of [Cl − ] i between individual neurons from young mice ( …”

“…It was later established that the shift from depolarizing GABA responses in young animals to hyperpolarizing responses in adult animals correlated with changes of the equilibrium potential of Cl − towards more negative potentials (Cherubini et al, 1991;Owens et al, 1996), with the onset of the expression of Cl − -extruding transporters such as KCC2 (Rivera et al, 1999), and with a decrease in the expression of Cl − -accumulating transporters such as NKCC1 (Yamada et al, 2004). However, the presumed decrease in [Cl − ] i occurring during development has not yet been visualized in brain slices or in vivo.…”

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…In addition, analysis of the gene expression profile of GG highlights developmental alterations of the balance between excitation and inhibition, with a prominent expression of mGluR5 and downregulation of several gammaaminobutyric acid (GABA)a receptor (GABA A R) subunits (including α1, α5, ß1, ß3, and δ), suggesting impairment of GABAergic inhibition [29,57,58]. A deregulation of the cation-chloride (NKCC1 and KCC2) cotransporters (CCTs), resembling the expression patterns observed in immature brain, has been reported in GGs [57,59], and may also actively contribute to the epileptogenicity of this tumor type via modulation of GABA receptors [60].…”

The role and the mechanism of γ-aminobutyric acid during central nervous system development

“…Indeed, NKCC1 transcripts were detected in the developing CNS as early as embryonal day 12.5, when expression was observed in scattered cells of the neuroepithelium [15] . By studying in Wistar rats at postnatal 1-21 d, Yamada found that in the early CNS development, the expression of NKCC1 mRNA is much higher than that in the later development, with the expression at the highest level in Wistar rats at postnatal 0-3 d [16] . The functional importance of NKCC1 in GABA signaling has been showed by targeted deletion [17] .…”