Cellular Mechanisms of Neuronal Cl Homeostasis and its Modulation by Neuronal Injury

  • A. A. Moorhouse
  • J. Nabekura


The function of the brain depends on the fine balance between inhibition and excitation of neurons. The polarity and amplitude of an inhibitory synaptic response depends on both the relative permeability of the receptor-channels involved, and also on the driving force for the permeant ions which is established by an array of active membrane transport proteins. At inhibitory synapses, the cation chloride co-transporters, including NKCC1 and KCC2, are particularly important in determining intracellular Cl concentrations and the efficacy of inhibitory synaptic responses. Recent experiments have shown that the expression and activity of these transporters can change, not only over development, but also in response to neuronal injury. In this article, we review the basic biophysical aspects and role of different transporters in neuronal Cl homeostasis and how the expression and function of these transporters, particularly KCC2, changes during development and in response to a wide range of models of neuronal injury. We also review recent data regarding the cellular and molecular mechanisms by which injury induced changes in KCC2 function may occur. Our review hopes to highlight the need for further investigation of these processes, to enable a greater understanding of developmental and pathological plasticity at inhibitory synapses, and to enable the potential development of novel therapeutic strategies to treat neuronal dysfunction.


Neuropathic Pain Neuronal Injury Inhibitory Synapse Ionotropic Receptor Inhibitory Synaptic Transmission 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Miho Watanabe for helpful comments.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Membrane Biophysics Laboratory, Department of Physiology, School of Medical SciencesUniversity of New South WalesSydneyAustralia
  2. 2.Division of Homeostatic Development, Department of Developmental PhysiologyNational Institute for Physiological SciencesOkazakiJapan

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