Kv4.3 Modulates the Distribution of hERG

This study examines the interaction between hERG and Kv4.3. The functional interaction between hERG and Kv4.3, expressed in a heterologous cell line, was studied using patch clamp techniques, western blot, immunofluorescence, and co-immunoprecipitation. Co-expression of Kv4.3 with hERG increased hERG current density (tail current after a step to +10 mV: 26 ± 3 versus 56 ± 7 pA/pF, p < 0.01). Kv4.3 co-expression also increased the protein expression and promoted the membrane localization of hERG. Western blot showed Kv4.3 increased hERG expression by Hsp70. hERG and Kv4.3 co-localized and co-immunoprecipitated in cultured 293 T cells, indicating physical interactions between hERG and Kv4.3 proteins in vitro. In addition, Hsp70 interacted with hERG and Kv4.3 respectively, and formed complexes with hERG and Kv4.3. The α subunit of I_to Kv4.3 can interact with and modify the localization of the α subunit of I_Kr hERG, thus providing potentially novel insights into the molecular mechanism of the malignant ventricular arrhythmia in heart failure.