Decreased sodium and increased transient outward potassium currents in iron-loaded cardiac myocytes - Implications for the arrhythmogenesis of human siderotic heart disease

Background-Patients with chronic iron overload may develop a cardiomyopathy manifested by ventricular arrhythmias and heart failure. We hypothesized t hat iron-loaded cardiomyocytes may have abnormal excitability. Methods and Results-We examined a new model of human iron overload, the Mon golian gerbil given repeated injections of iron dextran, In ventricular myo cytes, we measured iron concentration and distribution, action potential, s odium and potassium currents, and sodium channel protein. We showed for the first time that (1) the iron content of gerbil ventricular cardiomyocytes was increased to amounts similar to those of patients with iron-induced car diomyopathy; (2) the overshoot and duration of the cardiac action potential decreased; (3) sodium current was reduced, steady-state inactivation was e nhanced, and single-channel currents were unchanged; and (4) transient outw ard potassium current was increased, but inwardly rectifying potassium curr ent was unchanged. Neonatal rat cardiomyocytes incubated with iron for 1 to 3 days showed similar changes, and levels of cardiac sodium channel protei ns were unchanged, Conclusions-Abnormal excitability and heterogeneous cardiac iron deposition may cause the arrhythmogenesis of human siderotic heart disease.