Somatodendritic surface expression of epitope-tagged and KChIP binding-deficient Kv4.2 channels in hippocampal neurons

Kv4.2 channels mediate a subthreshold-activating somatodendritic A-type current (I(SA)) in hippocampal neurons. We examined the role of accessory Kv channel interacting protein (KChIP) binding in somatodendritic surface expression and activity-dependent decrease in the availability of Kv4.2 channels. For this purpose we transfected cultured hippocampal neurons with cDNA coding for Kv4.2 wild-type (wt) or KChIP binding-deficient Kv4.2 mutants. All channels were equipped with an externally accessible hemagglutinin (HA)-tag and an EGFP-tag, which was attached to the C-terminal end. Combined analyses of EGFP self-fluorescence, surface HA immunostaining and patch-clamp recordings demonstrated similar dendritic trafficking and functional surface expression for Kv4.2[wt](HA,EGFP) and the KChIP binding-deficient Kv4.2[A14K](HA,EGFP). Coexpression of exogenous KChIP2 augmented the surface expression of Kv4.2[wt](HA,EGFP) but not Kv4.2[A14K](HA,EGFP). Notably, activity-dependent decrease in availability was more pronounced in Kv4.2[wt](HA,EGFP) + KChIP2 coexpressing than in Kv4.2[A14K](HA,EGFP) + KChIP2 coexpressing neurons. Our results do not support the notion that accessory KChIP binding is a prerequisite for dendritic trafficking and functional surface expression of Kv4.2 channels, however, accessory KChIP binding may play a potential role in Kv4.2 modulation during intrinsic plasticity processes.