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 that iron-loaded cardiomyocytes may have abnormal excitability.


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.
Kuryshev
Y A
YA
Rammelkamp Center for Education and Research, MetroHealth Campus, Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA.
Brittenham
G M
GM
Fujioka
H
H
Kannan
P
P
Shieh
C C
CC
Cohen
S A
SA
Brown
A M
AM
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005849:Gerbillinae; D006801:Humans; D017136:Ion Transport; D019190:Iron Overload / Q000139:chemically induced / Q000150:complications*; D007505:Iron-Dextran Complex / Q000633:toxicity; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
D015221:Potassium Channels; D015222:Sodium Channels; D007505:Iron-Dextran Complex; D012964:Sodium; D011188:Potassium