TGF-β ₁ -Mediated Fibrosis and Ion Channel Remodeling Are Key Mechanisms in Producing the Sinus Node Dysfunction Associated With <i>SCN5A</i> Deficiency and Aging

Abstract

These results implicate a tissue degeneration triggered by Nav1.5 deficiency manifesting as a TGF-β(1)-mediated fibrosis accompanied by electric remodeling in the sinus node dysfunction associated with Scn5a disruption or aging. The latter effects interact to produce the most severe phenotype in old Scn5a(+/-) mice. In demonstrating this, our findings suggest a novel regulatory role for Nav1.5 in cellular biological processes in addition to its electrophysiologic function.