γ-Aminobutyric acid, a major inhibitory neurotransmitter within the adult central nervous system, is also known to be excitatory at early developmental stages due to the elevated intracellular Cl− concentration. This functional change is primarily attributable to a K+-Cl− cotransporter, KCC2, the expression of which is developmentally regulated in neurons. However, little detail information is available concerning the intracellular regulation of KCC2 function. Here, we identify an interaction between KCC2 and brain-type creatine kinase by means of yeast two-hybrid screening. This interaction, which was also detected in cultured cells and brain extracts, might contribute to KCC2-mediated modulation of Cl− homeostasis.
