The KCl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in the rat hippocampus

Immunocytochemical visualization of the neuron-specific K⁺/Cl^- cotransporter, KCC2, at the cellular and subcellular level revealed an area- and layer-specific diffuse labelling, and a discrete staining outlining the somata and dendrites of some interneurons in all areas of the rat hippocampus. KCC2 was highly expressed in parvalbumin-containing interneurons, as well as in subsets of calbindin, calretinin and metabotropic glutamate receptor 1a-immunoreactive interneurons. During the first 2 postnatal weeks, an increase of KCC2 staining was observed in the molecular layer of the dentate gyrus, correlating temporally with the arrival of entorhinal cortical inputs. Subcellular localization demonstrated KCC2 in the plasma membranes. Immunoreactivity in principal cells was responsible for the diffuse staining found in the neuropil. In these cells, KCC2 was detected primarily in dendritic spine heads, at the origin of spines and, at a much lower level on the somata and dendritic shafts. KCC2 expression was considerably higher in the somata and dendrites of interneurons, most notably of parvalbumin-containing cells, as well as in the thorny excrescences of CA3 pyramidal cells and in the spines of spiny hilar and stratum lucidum interneurons. The data indicate that KCC2 is highly expressed in the vicinity of excitatory inputs in the hippocampus, perhaps in close association with extrasynaptic GABA_A receptors. A high level of excitation is known to lead to a simultaneous net influx of Na⁺ and Cl^-, as evidenced by dendritic swelling. KCC2 located in the same microenvironment may provide a Cl^- extrusion mechanism to deal with both ion and water homeostasis in addition to its role in setting the driving force of Cl^- currents involved in fast postsynaptic inhibition.