Kv4.2 mRNA Abundance and A-Type K⁺Current Amplitude Are Linearly Related in Basal Ganglia and Basal Forebrain Neurons

Abstract

A-type K(+) currents are key determinants of repetitive activity and synaptic integration. Although several gene families have been shown to code for A-type channel subunits, recent studies have suggested that Kv4 family channels are the principal contributors to A-type channels in the somatodendritic membrane of mammalian brain neurons. If this hypothesis is correct, there should be a strong correlation between Kv4 family mRNA and A-type channel protein or aggregate channel currents. To test this hypothesis, quantitative single-cell reverse transcription-PCR analysis of Kv4 family mRNA was combined with voltage-clamp analysis of A-type K(+) currents in acutely isolated neurons. These studies revealed that Kv4.2 mRNA abundance was linearly related to A-type K(+) current amplitude in neostriatal medium spiny neurons and cholinergic interneurons, in globus pallidus neurons, and in basal forebrain cholinergic neurons. In contrast, there was not a significant correlation between estimates of Kv4.1 or Kv4.3 mRNA abundance and A-type K(+) current amplitudes. These results argue that Kv4.2 subunits are major constituents of somatodendritic A-type K(+) channels in these four types of neuron. In spite of this common structural feature, there were significant differences in the voltage dependence and kinetics of A-type currents in the cell types studied, suggesting that other determinants may create important functional differences between A-type K(+) currents.

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

“…Rat DRG neurons express a diverse population of K + channel types, exhibiting as many as 6 subtypes of currents distinguishable both by voltage dependence and pharmacology (Gold et al, 1996). Three of these currents, exhibit rapid to slow rates of activation (Fedulova et al, 1998) and inactivation (Fedulova et al, 1998,Everill et al, 1998) and correspond to Kv4 subtypes (Pongs, 1992;Tkatch et al, 2000), Kv1.2 and Kv1.4 types of K + channels (Ishikawa et al, 1999). The remaining currents are non-inactivating, delayed rectifier type (Gold et al, 1996;Ishikawa et al, 1999).…”

KChIPs and Kv4 α Subunits as Integral Components of A-Type Potassium Channels in Mammalian Brain

“…Immunoreactivity for Kv4.3 and KChIP1 ( C) is concentrated in what appear to be medium-sized striatal interneurons, whereas immunoreactivity for KChIP4 can be observed in very large, multipolar interneurons. (Song et al, 1998;Tkatch et al, 2000;Liss et al, 2001;Lien et al, 2002), does not hold for all cell types, in that hippocampal dentate granule and CA3 pyramidal cells and cerebellar granule cells express high levels of colocalized Kv4.2 and Kv4.3. Coimmunoprecipitation analysis in detergent-solubilized hippocampal membranes revealed that all four KChIPs coassociate with Kv4 ␣ subunits in hippocampal membranes, confirming that the KChIPs are tightly associated with Kv4 ␣ subunits in native brain A-type channel complexes.…”

Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats

“…However, several studies reported a straight relation between A-type K+ currents and Kv4 channels in neostriatal neurons (Tkatch et al 2000). Kv4 channels in the spiny neurons of the striatal medium regulate b-AP (Day et al 2008) and participate in clustering and firing bursting patterns (Falk et al 2006).…”