Abstract
The Kv4 family of voltage-gated K+ channels underlie the fast transient (A-type) outward K+ current. Although A-type currents are critical to determine somato-dendritic integration in central neurons, relatively little is known about the precise subcellular localisation of the underlying channels in hippocampal circuits. Using histoblot and immunoelectron microscopic techniques, we investigated the expression, regional distribution and subcellular localisation of Kv4.2 and Kv4.3 in the adult brain, as well as the ontogeny of their expression during postnatal development. Histoblot demonstrated that Kv4.2 and Kv4.3 proteins were widely expressed in the brain, with mostly non-overlapping patterns. During development, levels of Kv4.2 and Kv4.3 increased with age but showed marked region- and developmental stage-specific differences. Immunoelectron microscopy showed that labelling for Kv4.2 and Kv4.3 was differentially present in somato-dendritic domains of hippocampal principal cells and interneurons, including the synaptic specialisation. Quantitative analyses indicated that most immunoparticles for Kv4.2 and Kv4.3 were associated with the plasma membrane in dendritic spines and shafts, and that the two channels showed very similar distribution patterns in spines of principal cells and along the surface of granule cells. Our data shed new light on the subcellular localisation of Kv4 channels and provide evidence for their non-uniform distribution over the plasma membrane of hippocampal neurons.
Highlights
Principal cells and interneurons of the hippocampus are fundamental for information processing in this brain region [1]
Immunoreactivity for Kv4.2 was strongest in the cerebellum and hippocampus (Figure 1A,B)
In the hippocampus, immunolabelling for Kv4.2 was strongest in the strata oriens and radiatum of the CA1 region and in the molecular layer of the dentate gyrus (Figure 1C,D)
Summary
Principal cells and interneurons of the hippocampus are fundamental for information processing in this brain region [1]. The main hippocampal trisynaptic circuit that relays cortical input to granule cells in the dentate gyrus on to pyramidal neurons in the cornu Ammonis 3 (CA3) region and to pyramidal neurons in the CA1 region is important for spatial navigation, memory consolidation and decision making [1] These and other functions of hippocampal neurons depend on their synchronous activity, which is controlled by organised excitatory and inhibitory inputs to dendritic spines and shafts and by intrinsic conductances that cause them to fire. Electrophysiological, pharmacological and immunohistochemical data suggest that a major component of the somato-dendritic A-type Kv current is formed by the Shal or Kv4 family [4,6,7] These channels are formed by four Kv4 α subunits (Kv4.1, Kv4.2 and Kv4.3), but only Kv4.2 and Kv4.3 are predominant in the brain. KChIPs regulate biophysical, biochemical and cell biological properties of Kv4 channels
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