I. Chudotvorova and A. Ivanov contributed equally to this work.
Early expression of KCC2 in rat hippocampal cultures augments expression of functional GABA synapses
Article first published online: 27 JUL 2005
The Journal of Physiology
Volume 566, Issue 3, pages 671–679, August 2005
How to Cite
Chudotvorova, I., Ivanov, A., Rama, S., Hübner, C. A., Pellegrino, C., Ben-Ari, Y. and Medina, I. (2005), Early expression of KCC2 in rat hippocampal cultures augments expression of functional GABA synapses. The Journal of Physiology, 566: 671–679. doi: 10.1113/jphysiol.2005.089821
- Issue published online: 27 JUL 2005
- Article first published online: 27 JUL 2005
- (Received 10 May 2005; accepted after revision 10 June 2005; first published online 16 June 2005)
The development of GABAergic synapses is associated with an excitatory to inhibitory shift of the actions of GABA because of a reduction of [Cl−]i. This is due to a delayed postnatal expression of the K+–Cl− cotransporter KCC2, which has low levels at birth and peaks during the first few postnatal weeks. Whether the expression of the cotransporter and the excitatory to inhibitory shift have other consequences on the operation of GABAA receptors and synapses is not yet known. We have now expressed KCC2 in immature neurones at an early developmental stage and determined the consequences on the formation of GABA and glutamate synapses. We report that early expression of the cotransporter selectively enhances GABAergic synapses: there is a significant increase of the density of GABAA receptors and synapses and an increase of the frequency of GABAergic miniature postsynaptic currents. The density of glutamate synapses and frequency of AMPA miniature postsynaptic currents are not affected. We conclude that the expression of KCC2 and the reduction of [Cl−]i play a critical role in the construction of GABAergic networks that extends beyond the excitatory to inhibitory shift of the actions of GABA.