Abstract: Objective To investigate the association of desmoplakin with the distribution and function of Nav1.5 by RNA
silencing technology in HL-1 cells. Methods HL-1 cells with desmoplakin expression suppression by RNA silencing were
examined for desmoplakin and Nav1.5 protein expressions by Western blotting, and the distribution and co-location of
desmoplakin and Nav1.5 protein were detected by immunoflurescence staining. Patch-clamp recording was applied to analyze
the changes in whole-cell sodium current after desmoplakin silencing. Results Compared with the untreated group and
negative control group, the cells with desmoplakin silencing showed obviously reduced expressions of desmoplakin and
Nav1.5 proteins. Co-localization of desmoplakin and Nav1.5 was detected at cell-cell contact in untreated and control
conditions, and desmoplakin expression silencing induced a drastic redistribution of Nav1.5 with decreased peak current
density (156.3±6.2 vs 41.8±3.1, n=6, P<0.05), a shift in voltage dependence of steady-state inactivation (-42 mV vs -61 mV, n=5, P<
0.05), and prolonged time of recovery from inactivation. Conclusion Desmoplakin silencing caused redistribution of Nav1.5
protein and also changes in its electrophysiological properties in HL-1 cells.