Modulation of K4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2.

The transient outward potassium current () is generated by the activation of K4 channels assembled with KChIP2 and other accessory subunits (DPP6 and KCNE2). To test the hypothesis that these subunits modify the channel pharmacology, we analyzed the electrophysiological effects of (3-(2-(3-phenoxyphenyl)acetamido)-2-naphthoic acid) (IQM-266), a new KChIP2 ligand, on the currents generated by K4.3/KChIP2, K4.

Identification of IQM-266, a Novel DREAM Ligand That Modulates K4 Currents.

Downstream Regulatory Element Antagonist Modulator (DREAM)/KChIP3/calsenilin is a neuronal calcium sensor (NCS) with multiple functions, including the regulation of A-type outward potassium currents ( ). This effect is mediated by the interaction between DREAM and K4 potassium channels and it has been shown that small molecules that bind to DREAM modify channel function. A-type outward potassium current ( ) is responsible of the fast repolarization of neuron action potentials and frequency of firing.