(Circulation. 1999;100:675-683.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Decreased Sodium and Increased Transient Outward Potassium Currents in Iron-Loaded Cardiac Myocytes
Implications for the Arrhythmogenesis of Human Siderotic Heart Disease
From the Rammelkamp Center for Education and Research (Y.A.K., G.M.B., P.K., C.-C.S., A.M.B.), MetroHealth Campus, and the Departments of Physiology and Biophysics (Y.A.K., A.M.B.), Medicine (G.M.G.), and Pathology (H.F.), Case Western Reserve University, Cleveland, Ohio, and Centocor Inc., Molvern, Pa. (S.A.C.).
Correspondence to Arthur Brown, MD, PhD, Rammelkamp Center R301, 2500 MetroHealth Drive, Cleveland, OH 44109-1998. E-mail abrown{at}research.mhmc.org
Background—Patients with chronic iron overload may develop a cardiomyopathy manifested by ventricular arrhythmias and heart failure. We hypothesized that iron-loaded cardiomyocytes may have abnormal excitability.
Methods and Results—We examined a new model of human iron overload, the Mongolian gerbil given repeated injections of iron dextran. In ventricular myocytes, we measured iron concentration and distribution, action potential, sodium 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 cardiomyopathy; (2) the overshoot and duration of the cardiac action potential decreased; (3) sodium current was reduced, steady-state inactivation was enhanced, and single-channel currents were unchanged; and (4) transient outward potassium current was increased, but inwardly rectifying potassium current was unchanged. Neonatal rat cardiomyocytes incubated with iron for 1 to 3 days showed similar changes, and levels of cardiac sodium channel proteins were unchanged.
Conclusions—Abnormal excitability and heterogeneous cardiac iron deposition may cause the arrhythmogenesis of human siderotic heart disease.
Key Words: iron overload • cardiomyopathy • gerbil • sodium channels • potassium channels
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