Chemoreceptor cells from rabbit carotid body (CB) exhibit transient outward currents reversibly inhibited by low PO₂. Molecular and functional dissection of the components of this outward currents indicates that at least two different channels (Kv4.3 and Kv3.4) contribute to this current. Furthermore, several lines of evidence support the conclusion that Kv4 channel subfamily members (either Kv4.3 alone or Kv4.3/Kv4.1 heteromultimers) are the oxygen sensitive K channels (KO₂) in rabbit CB chemoreceptor cells. However, the pharmacological characterization of these currents shows that they are almost completely blocked by high external TEA concentrations, while Kv4 channels have been shown to be TEA-insensitive. We hypothesized that the expression of regulatory subunits in chemoreceptor cells could modify TEA sensitivity of Kv4 channels. We explored the presence of Kv4-regulatory subunits in rabbit CB chemoreceptor cells and their ability to modify the pharmacological profile of Kv4 channels in heterologous expression systems and in native tissue. We found that coexpression of Kv4.3 channels with DPPX in HEK cells leads to kinetic modifications of the heteromultimers, that also exhibit sensitivity to block by TEA. The physiological role of this association was explored in CB chemoreceptor cells, by studying the effects of DPPX knock-down by electroporating chemoreceptor cells with siRNA against DPPX. Outward K⁺ currents recorded from transfected CB chemoreceptor cells exhibited a significant decrease in their TEA sensitivity, suggesting that DPPX association contributes to the "atypical" pharmacological profile of Kv4 currents. Supported by ISCIII grants R006/009 (Red Heracles) and PI041044, MEC grant BFU2004-05551 and JCyL grant VA011C05.