Expression and developmental regulation of the K+-Cl− cotransporter KCC2 in the cochlear nucleus

KCC2 is a neuron-specific Cl− transporter whose role in adult central neurons is to maintain low intracellular Cl− concentrations and, therefore, generate an inward-directed electrochemical gradient for Cl− needed for the hyperpolarizing responses to the inhibitory amino acids GABA and glycine. We report that the KCC2 protein is intensely expressed in CN neurons and preferentially associated with plasma membrane domains, consistent with GABA and glycinergic-mediated inhibition in this auditory nucleus. Postnatal KCC2 expression and distribution patterns are similar in developing and adult CN neurons and do not match the time course of GABergic or glycinergic synaptogenesis. Therefore, in the CN, neither KCC2 protein upregulation nor progressive integration in the plasma membrane seem to be involved in KCC2 developmental regulation. Considering that GABA and glycine are depolarizing during early postnatal development, it is conceivable that KCC2 is in place but inactive during early postnatal development in the CN and becomes active as inhibitory synaptogenesis proceeds. This notion is supported by the finding that the phosphorylation state of KCC2 differs from developing to adult CN, with the phosphorylated form predominating in the latter.