Kv4.2 channels mediate the neuronal subthreshold A-type current, which controls dendritic excitability. In temporal lobe epilepsy dendritic excitability is increased due to a reduced availability of functional Kv4.2 channels. Native Kv4.2 channel complexes may contain Kv Channel Interacting Proteins (KChIPs) and Dipeptidyl aminopeptidase (DPP)-like proteins as accessory subunits. In heterologous expression systems both subunits have been shown to modulate gating parameters and enhance functional surface expression of Kv4 channel complexes. We ask if the effects observed in heterologous expression systems reflect a physiological role of accessory subunits in Kv4.2 channel trafficking, targeting and function in nerve cells. We transfected cultured rat hippocampal neurons with cDNA coding for Kv4.2 wild-type or the KChIP binding-deficient mutant Kv4.2A14K. Both channels were decorated with an external HA-and a C-terminal EGFP-tag. Combined analysis of EGFP self-fluorescence and HA immunostaining showed that Kv4.2A14K-HA-EGFP is transported into dendrites and gets to the surface membrane. These results suggest that Kv4.2 interaction with KChIP is not absolutely essential for the surface expression of somatodendritic A-type channels.

Supported by the Deutsche Forschungsgemeinschaft (SFB444A8)