NKCC1 cotransporter inactivation underlies embryonic development of chloride-mediated inhibition in mouse spinal motoneuron
The Journal of Physiology. 2008-02-15; 586(4): 1059-1075
DOI: 10.1113/jphysiol.2007.146993
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1. J Physiol. 2008 Feb 15;586(4):1059-75. Epub 2007 Dec 20.
NKCC1 cotransporter inactivation underlies embryonic development of
chloride-mediated inhibition in mouse spinal motoneuron.
Delpy A(1), Allain AE, Meyrand P, Branchereau P.
Author information:
(1)Centre de Neuroscience Intégratives et Cognitives, Université Bordeaux and
CNRS, UMR 5228, Avenue des Facultés, 33405 Talence cedex, France.
Early in development, GABA and glycine exert excitatory action that turns to
inhibition due to modification of the chloride equilibrium potential (E(Cl))
controlled by the KCC2 and NKCC1 transporters. This switch is thought to be due
to a late expression of KCC2 associated with a NKCC1 down-regulation. Here, we
show in mouse embryonic spinal cord that both KCC2 and NKCC1 are expressed and
functional early in development (E11.5-E13.5) when GABA(A) receptor activation
induces strong excitatory action. After E15.5, a switch occurs rendering GABA
unable to provide excitation. At these subsequent stages, NKCC1 becomes both
inactive and less abundant in motoneurons while KCC2 remains functional and
hyperpolarizes E(Cl). In conclusion, in contrast to other systems, the
cotransporters are concomitantly expressed early in the development of the mouse
spinal cord. Moreover, whereas NKCC1 follows a classical functional extinction,
KCC2 is highly expressed throughout both early and late embryonic life.
DOI: 10.1113/jphysiol.2007.146993
PMCID: PMC2375629
PMID: 18096599 [Indexed for MEDLINE]