Kuryshev Y A, Brittenham G M, Fujioka H, Kannan P, Shieh C C, Cohen S A, Brown A M
Rammelkamp Center for Education and Research, MetroHealth Campus, Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA.
Circulation. 1999 Aug 10;100(6):675-83. doi: 10.1161/01.cir.100.6.675.
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.
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.
Abnormal excitability and heterogeneous cardiac iron deposition may cause the arrhythmogenesis of human siderotic heart disease.
慢性铁过载患者可能会发展为以室性心律失常和心力衰竭为表现的心肌病。我们推测铁负荷过重的心肌细胞可能具有异常兴奋性。
我们研究了一种新的人类铁过载模型，即反复注射右旋糖酐铁的蒙古沙鼠。在心室肌细胞中，我们测量了铁浓度和分布、动作电位、钠电流和钾电流以及钠通道蛋白。我们首次表明：（1）沙鼠心室心肌细胞的铁含量增加至与铁诱导性心肌病患者相似的水平；（2）心脏动作电位的超射值和持续时间缩短；（3）钠电流减少，稳态失活增强，单通道电流不变；（4）瞬时外向钾电流增加，但内向整流钾电流不变。用铁孵育1至3天的新生大鼠心肌细胞表现出类似变化，心脏钠通道蛋白水平不变。
异常兴奋性和心脏铁沉积不均一性可能导致人类铁性心脏病的心律失常发生。
