In patch-clamp experiments, co-expression of trafficking deficient mutants Kir2.1¿314-315 or Kir2.1R44A/R46A with wildtype (WT) NaV1.5WT in heterologous cells reduced INa, compared to NaV1.5WT alone or co-expressed with Kir2.1WT In cell surface biotinylation experiments, expression of Kir2.1¿314-315 reduced NaV1.5 channel surface expression. Glycosylation analysis suggested that NaV1.5WT and Kir2.1WT channels associate early in their biosynthetic pathway, and fluorescence recovery after photobleaching experiments demonstrated that co-expression with Kir2.1 increased cytoplasmic mobility of NaV1.5WT, and vice versa, whereas co-expression with Kir2.1¿314-315 reduced mobility of both channels. Viral gene transfer of Kir2.1¿314-315 in adult rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) reduced Read more »