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Cl − uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1
Author(s) -
Yamada Junko,
Okabe Akihito,
Toyoda Hiroki,
Kilb Werner,
Luhmann Heiko J.,
Fukuda Atsuo
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.062471
Subject(s) - neocortex , cotransporter , depolarization , gabaergic , inhibitory postsynaptic potential , gabaa receptor , messenger rna , biology , reversal potential , intracellular , medicine , endocrinology , chemistry , neurotransmitter , gamma aminobutyric acid , receptor , neuroscience , microbiology and biotechnology , electrophysiology , biochemistry , patch clamp , central nervous system , gene , organic chemistry , sodium
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.