title: NKCC1 downregulation induces hyperpolarizing shift of GABA responsiveness at near term fetal stages in rat cultured dorsal root ganglion neurons.
abstract: BACKGROUND
  GABAA receptor-mediated neurotransmission is greatly influenced by cation-chloride cotransporter activity during developmental stages. In embryonic neurons Na-K-2Cl (NKCC1) cotransporters mediate active chloride uptake, thus increasing the intracellular chloride concentration associated with GABA-induced depolarization. At fetal stages near term, oxytocin-induced NKCC1 downregulation has been implicated in the developmental shift from depolarizing to hyperpolarizing GABA action. Mature dorsal root ganglion neurons (DRGN), however, express high NKCC1 levels and maintain high intracellular chloride levels with consequent GABA-induced depolarization.
  
  
  RESULTS
  Gramicidin-perforated patch-clamp recordings were used to assess the developmental change in chloride homeostasis in rat cultured small DRGN at the embryonic day 16 (E16) and 19 (E19). The results were compared to data previously obtained in fetal DRGN at E14 and in mature cells. A significant NKCC1 downregulation, leading to reduction in excitatory GABAergic transmission, was observed at E16 and E19.
  
  
  CONCLUSIONS
  These results indicate that NKCC1 activity transiently decreases in DRGN at fetal stages near term. This developmental shift in GABAergic transmission may contribute to fetal analgesia and neuroprotection at birth.
authors.affiliation: Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven (KU Leuven), Louvain, Belgium. jo.nsimy@gmail.com.|Neurology Unit, Department of Medicine, Faculty of Sciences, University of Fribourg, Chemin du Musée, 5, Fribourg, 1700, Switzerland. jo.nsimy@gmail.com.
authors.forename: Joelle N
authors.initials: JN
authors.lastname: Chabwine
authors.affiliation: Laboratory of Ion Channel Research and TRP Channel Research Platform (TRPLe), Department of Cellular and Molecular Medicine, KU Leuven, Louvain, Belgium. karel.talavera@med.kuleuven.be.
authors.forename: Karel
authors.initials: K
authors.lastname: Talavera
authors.affiliation: Laboratory of Neurobiology, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven, Louvain, Belgium. ludo.vandenbosch@vib-kuleuven.be.|VIB, Vesalius Research Center, KU Leuven, Louvain, Belgium. ludo.vandenbosch@vib-kuleuven.be.
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
authors.affiliation: Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven (KU Leuven), Louvain, Belgium. geert.callewaert@med.kuleuven.be.
authors.forename: Geert
authors.initials: G
authors.lastname: Callewaert
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000187:drug effects / Q000196:embryology* / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017208:Rats, Wistar; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002712:Chlorides; C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D005680:gamma-Aminobutyric Acid