Abstract
GABA is the principal inhibitory neurotransmitter in the mature brain, but during early postnatal development the elevated [Cl−]i in immature neocortical neurones causes GABAA receptor activation to be depolarizing. The molecular mechanisms underlying this intracellular Cl− accumulation remain controversial. Therefore, the GABA reversal potential (EGABA) 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 EGABA 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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Dates
Type | When |
---|---|
Created | 21 years, 4 months ago (April 19, 2004, 8:45 p.m.) |
Deposited | 1 year, 10 months ago (Oct. 14, 2023, 3:33 p.m.) |
Indexed | 5 days, 4 hours ago (Aug. 23, 2025, 9:20 p.m.) |
Issued | 21 years, 2 months ago (June 1, 2004) |
Published | 21 years, 2 months ago (June 1, 2004) |
Published Online | 21 years, 2 months ago (June 14, 2004) |
Published Print | 21 years, 2 months ago (June 1, 2004) |
@article{Yamada_2004, title={Cl− uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1}, volume={557}, ISSN={1469-7793}, url={http://dx.doi.org/10.1113/jphysiol.2004.062471}, DOI={10.1113/jphysiol.2004.062471}, number={3}, journal={The Journal of Physiology}, publisher={Wiley}, author={Yamada, Junko and Okabe, Akihito and Toyoda, Hiroki and Kilb, Werner and Luhmann, Heiko J. and Fukuda, Atsuo}, year={2004}, month=jun, pages={829–841} }