Nonsynaptic glycine release is involved in the early KCC2 expression
Devel Neurobio. 2015-11-03; 76(7): 764-779
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Allain AE(1), Cazenave W(1), Delpy A(1), Exertier P(1), Barthe C(2), Meyrand P(3), Cattaert D(1), Branchereau P(1).
(1)Univ. Bordeaux, INCIA, UMR 5287, Site Talence, F33615 Pessac cedex, France. CNRS, INCIA, UMR 5287, Site Talence, F33615 Pessac cedex, France.
(2)Univ. Bordeaux, Laboratoire De Biotechnologie Des Protéines Recombinantes À Visée Santé, EA 4135, Bordeaux, F-33076, Bordeaux.
(3)Univ. Bordeaux, IMN, UMR 5293, Site Talence, F33615 Pessac cedex, France. CNRS, IMN, UMR 5293, Site Talence, F33615, Pessac cedex, France.
The cation-chloride co-transporters are important regulators of the cellular
Cl(-) homeostasis. Among them the Na(+) -K(+) -2Cl(-) co-transporter (NKCC1) is
responsible for intracellular chloride accumulation in most immature brain
structures, whereas the K(+) -Cl(-) co-transporter (KCC2) extrudes chloride from
mature neurons, ensuring chloride-mediated inhibitory effects of GABA/glycine. We
have shown that both KCC2 and NKCC1 are expressed at early embryonic stages
(E11.5) in the ventral spinal cord (SC). The mechanisms by which KCC2 is
prematurely expressed are unknown. In this study, we found that chronically
blocking glycine receptors (GlyR) by strychnine led to a loss of KCC2 expression,
without affecting NKCC1 level. This effect was not dependent on the firing of
Na(+) action potentials but was mimicked by a Ca(2+) -dependent PKC blocker.
Blocking the vesicular release of neurotransmitters did not impinge on strychnine
effect whereas blocking volume-sensitive outwardly rectifying (VSOR) chloride
channels reproduced the GlyR blockade, suggesting that KCC2 is controlled by a
glycine release from progenitor radial cells in immature ventral spinal networks.
Finally, we showed that the strychnine treatment prevented the maturation of
rhythmic spontaneous activity. Thereby, the GlyR-activation is a necessary
developmental process for the expression of functional spinal motor networks. ©
2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 764-779, 2016.