Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the emergence of low intracellular chloride
Article first published online: 20 NOV 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Comparative Neurology
Volume 468, Issue 1, pages 57–64, 1 January 2004
How to Cite
Stein, V., Hermans-Borgmeyer, I., Jentsch, T. J. and Hübner, C. A. (2004), Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the emergence of low intracellular chloride. J. Comp. Neurol., 468: 57–64. doi: 10.1002/cne.10983
- Issue published online: 20 NOV 2003
- Article first published online: 20 NOV 2003
- Manuscript Accepted: 31 JUL 2003
- Manuscript Revised: 20 JUN 2003
- Manuscript Received: 26 MAR 2003
- Deutsche Forschungsgemeinschaft. Grant Numbers: HU 800/1-1, JE 164/4-4
- K+Cl− cotransport;
- synaptic inhibition;
Fast synaptic inhibition in the adult central nervous system (CNS) is mediated by GABA and glycine. During early development GABA acts as an excitatory neurotransmitter, which is deemed to be important for the maturation of the CNS. During development GABAergic responses undergo a switch from excitatory to inhibitory. This switch is correlated with upregulation of KCC2, the neuronal isoform of the potassium-chloride cotransporter family. KCC2 lowers the intraneuronal chloride concentration below its electrochemical equilibrium. KCC2 activity is thought to depend on phosphorylation by endogenous tyrosine kinases. Here, we analyzed the expression pattern of KCC2 during murine embryonic and postnatal development by in situ hybridization and Western blot analysis. KCC2 expression paralleled neuronal differentiation and preceded the decline of the GABA reversal potential (EGABA) in spinal cord motoneurons and hippocampal pyramidal cells. The adult inhibitory response to GABA was established earlier in the spinal cord than in the hippocampus. Phosphorylated KCC2 protein was already present early in development when the functional GABA switch had not yet occurred. Thus, tyrosine-phosphorylation seems to be less important than the transcriptional upregulation of KCC2. J. Comp. Neurol. 468:57–64, 2004. © 2003 Wiley-Liss, Inc.