The Eelectrophysiological Effects of Iron Overload on the Heart

Chronic iron overload (CIO) in patients leads to a cardiomyopathy characterized by conduction defects, including bradyarrhythmias. Using a murine model of CIO, we explored the effects of iron loading on the electrophyisology of the heart. Telemetric heart rate was reduced in conscious CIO mice compared to controls. Similarly, heart rates were depressed in both isolated CIO hearts and CIO mice following autonomic blockade, suggesting an intrinsic impairment of the SA node (SAN). Indeed, spontaneous action potential frequency was reduced in CIO SAN myocytes. The depressed pacing rate in CIO SAN myocytes was linked to reduced L-type Ca2+ current (ICa,L) density and a rightward shift in ICa,L activation, suggesting a selective reduction in α1D-mediated ICa,L. Western blot analysis demonstrates that the α1D isoform was reduced by ~ 89% in CIO atrial tissue. Therefore, the conduction defects under conditions of CIO are due to reductions in Cav1.3 channel expression in atrial tissue.MAS