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

Authors: Yamada, J  Okabe, A  Toyoda, H  Kilb, W  Luhmann, HJ  Fukuda, A 
Citation: Yamada J, etal., J Physiol. 2004 Jun 15;557(Pt 3):829-41. Epub 2004 Apr 16.
Pubmed: (View Article at PubMed) PMID:15090604
DOI: Full-text: DOI:10.1113/jphysiol.2004.062471

GABA is the principal inhibitory neurotransmitter in the mature brain, but during early postnatal development the elevated [Cl(-)](i) in immature neocortical neurones causes GABA(A) receptor activation to be depolarizing. The molecular mechanisms underlying this intracellular Cl(-) accumulation remain controversial. Therefore, the GABA reversal potential (E(GABA)) or [Cl(-)](i) in early postnatal rat neocortical neurones was measured by the gramicidin-perforated patch-clamp method, and the relative expression levels of the cation-Cl(-) cotransporter mRNAs (in the same cells) were examined by semiquantitative single-cell multiplex RT-PCR to look for statistical correlations with [Cl(-)](i). The mRNA expression levels were positively (the Cl(-) accumulating Na(+),K(+)-2Cl(-) cotransporter NKCC1) or negatively (the Cl(-) extruding K(+)-Cl(-) cotransporter KCC2) correlated with [Cl(-)](i). NKCC1 mRNA expression was high in early postnatal days, but decreased during postnatal development, whereas KCC2 mRNA expression displayed the opposite pattern. [Cl(-)](i) and 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.

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CRRD Object Information
CRRD ID: 1580436
Created: 2006-07-31
Species: All species
Last Modified: 2006-07-31
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.