Abstract
The type 2 potassium–chloride cotransporter (KCC2) is the main regulator of intracellular chloride concentration in CNS neurons, and plays a crucial role in spine development that is independent of its ion cotransport function. The expression pattern of KCC2 is upregulated during postnatal development showing area and layer-specific differences in distinct brain areas. We examined the regional and ultrastructural localisation of KCC2 in various areas of developing neocortex and paleocortex during the first two postnatal weeks. Light-microscopy examination revealed diffuse neuropil and discrete funnel-shaped dendritic labelling in the piriform and entorhinal cortices at birth. Subsequently, during the beginning of the first postnatal week, diffuse KCC2 labelling gradually started to appear in the superficial layers of the neocortex while the punctate-like labelling of dendrites in the piriform, entorhinal and perirhinal cortices become more pronounced. By the end of the first postnatal week, discrete dendritic expression of KCC2 was visible in all neocortical and paleocortical areas. The expression level did not change during the second postnatal week suggesting that, in contrast to hippocampus, adult pattern of KCC2 in the cortical cells is already established by the end of the first postnatal week. Quantitative electron microscopy examination revealed that in superficial layers of both neo- and paleocortex, the majority of KCC2 signal was plasma membrane associated but the number of transport vesicle-associated immunosignal increased with development. In deep layers, KCC2 immunolabeling was evenly distributed in plasma membrane and transport vesicles showing no obvious change with maturation. The number of KCC2 immunogold particles increased in dendritic spines with no association with synapses. This observation points to the dual role of KCC2 in spine genesis and ion cotransport.
Highlights
Fast hyperpolarizing inhibition in the central nervous system (CNS) is mediated by ligand-gated anion channels (i.e. GABAA and glycine receptors) that gate currents predominantly carried by Cl- and to a lesser extent to HCO3(Farrant and Kaila 2007; Kaila 1994)
The type 2 potassium–chloride cotransporter (KCC2) is the main regulator of intracellular chloride concentration in CNS neurons, and plays a crucial role in spine development that is independent of its ion cotransport function
The expression level did not change during the second postnatal week suggesting that, in contrast to hippocampus, adult pattern of KCC2 in the cortical cells is already established by the end of the first
Summary
Fast hyperpolarizing inhibition in the central nervous system (CNS) is mediated by ligand-gated anion channels (i.e. GABAA and glycine receptors) that gate currents predominantly carried by Cl- and to a lesser extent to HCO3(Farrant and Kaila 2007; Kaila 1994). The action of GABAA and glycine receptors highly depends on the intracellular chloride concentration ([Cl-]i). The vast majority of the neurons has low [Cl-]i resulting in Cl- influx during channel opening and subsequent hyperpolarization of the cell (Eccles 1966; Kaila 1994). Brain Struct Funct (2014) 219:527–538 glycine receptor causes an outward flux of Cl- that depolarizes the cell (Cherubini et al 1991; Ehrlich et al 1999; Zhang et al 1990). Potassium–chloride co-transporter 2 (KCC2), found exclusively in neuronal cells, is responsible for the [Cl-]i homeostasis by constantly transporting K? and Cl- out of the cell (Rivera et al 1999; Payne et al 1996; Lu et al 1999; DeFazio et al 2000)
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