Kv4.2 channels are the principal mediators of the fast transient outward K+ current (Itof) in the heart and the A-type current (IA) in the nervous system, both of which play a relevant role in shaping cardiac action potentials and neuronal excitability. This review focuses on how interactions with ancillary subunits, such as potassium channel interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPPs), beyond regulating trafficking, membrane expression, and gating properties of Kv4.2 channels, significantly influence channel drug response, demonstrating that Kv4.2 does not represent a fixed pharmacological entity but rather a dynamic macromolecular complex whose drug responsiveness depends on its subunit composition. Understanding this accessory subunit-dependent modulation is important, as the pharmacological profile of Kv4.2-containing channels may differ depending on the predominant accessory subunit composition in each tissue.
Villatoro-Gómez et al. (Tue,) studied this question.