Modulation of Iron Uptake in Heart by L-Type Ca Channel Modifiers Possible Implications in Iron Overload

نویسندگان

  • Peter H. Backx
  • Robert G. Tsushima
  • Alan D. Wickenden
  • Ron A. Bouchard
  • Gavin Y. Oudit
  • Peter P. Liu
چکیده

Heart failure is the leading cause of mortality in patients with transfusional iron (Fe) overload in which myocardial iron uptake ensues via a transferrin-independent process. We examined the ability of L-type Ca channel modifiers to alter Fe uptake by isolated rat hearts and ventricular myocytes. Perfusion of rat hearts with 100 nmol/L Fe and 5 mmol/L ascorbate resulted in specific Fe uptake of 20.461.9 ng of Fe per gram dry wt. Abolishing myocardial electrical excitability with 20 mmol/L KCl reduced specific Fe uptake by 6067% (P,0.01), which suggested that a component of myocardial Fe uptake depends on membrane voltage. Accordingly, Fe uptake was inhibited by 10 mmol/L nifedipine (45612%, P,0.02) and 100 mmol/L Cd (8663%; P,0.001) while being augmented by 100 nmol/L Bay K 8644 (61618%, P,0.01) or 100 nmol/L isoproterenol (40612%, P,0.05). By contrast, uptake of 100 nmol/L ferric iron (Fe) was significantly lower (1.460.3 ng Fe per gram dry wt; P,0.001) compared with divalent iron. These data suggest that a component of Fe uptake into heart occurs via the L-type Ca channel in myocytes. To investigate this further, the effects of Fe on cardiac myocyte L-type Ca currents were measured. In the absence of Ca, noninactivating nitrendipine-sensitive Fe currents were recorded with 15 mmol/L [Fe]o. Low concentrations of Fe 21 enhanced Ca current amplitude and slowed inactivation rates, which was consistent with Fe entry into the cell, whereas higher Fe levels caused dose-dependent decreases in peak current. Fe had no effect on current amplitude or decay. Combined, our data suggest that myocardial Fe uptake occurs via L-type Ca channels and that blockade of these channels might be useful in the treatment of patients with excessive serum iron levels. (Circ Res. 1999;84:1302-1309.)

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Modulation of iron uptake in heart by L-type Ca2+ channel modifiers: possible implications in iron overload.

Heart failure is the leading cause of mortality in patients with transfusional iron (Fe) overload in which myocardial iron uptake ensues via a transferrin-independent process. We examined the ability of L-type Ca2+ channel modifiers to alter Fe2+ uptake by isolated rat hearts and ventricular myocytes. Perfusion of rat hearts with 100 nmol/L 59Fe2+ and 5 mmol/L ascorbate resulted in specific 59F...

متن کامل

Iron Overload and Apoptosis of HL-1 Cardiomyocytes: Effects of Calcium Channel Blockade

BACKGROUND Iron overload cardiomyopathy that prevails in some forms of hemosiderosis is caused by excessive deposition of iron into the heart tissue and ensuing damage caused by a raise in labile cell iron. The underlying mechanisms of iron uptake into cardiomyocytes in iron overload condition are still under investigation. Both L-type calcium channels (LTCC) and T-type calcium channels (TTCC) ...

متن کامل

Iron overload decreases CaV1.3-dependent L-type Ca2+ currents leading to bradycardia, altered electrical conduction, and atrial fibrillation.

BACKGROUND Chronic iron overload (CIO) is associated with blood disorders such as thalassemias and hemochromatosis. A major prognostic indicator of survival in patients with CIO is iron-mediated cardiomyopathy characterized by contractile dysfunction and electrical disturbances, including slow heart rate (bradycardia) and heart block. METHODS AND RESULTS We used a mouse model of CIO to invest...

متن کامل

Hydrophilic Phytochelators in Iron Overload Condition

Background: Iron overload can cause many complications and damage many organs as well as physiologic functions. Consumption of phetochemicals and flavonoids with iron chelating ability, instead of synthetic iron chelators, can be less harmful and more effective. The aim of this review is to investigate hydrophilic phytochelators in iron overload condition. Methods: In this review, the possible ...

متن کامل

Possible protective effect of naringin (a citrus bioflavonoid) against kidney injury induced by γ-irradiation and /or iron overload in male rats

Background: the supplementation of natural antioxidants such plant flavonoids may counteract the deleterious actions of gamma-irradiation and iron overload. Material and Methods: the protective effect of naringin (NIN) against kidney injury induced by γ-irradiation (IRR) (6.5 Gy) and/or iron dextran (ID) (50 mg/kg. b. w) has been studied in rats given 80 mg/kg b.w of NIN for 14 days before, and...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 1999