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.