Iron Administration Affects Cardiac Calcium Channel Expression in Mice: The Role of Cardiac Calcium Channel Expression in The Heart of Iron Overload Mice Model

Mas Rizky Anggun Adipurna Syamsunarno, Alif Bagus Rakhimullah, Uni Gamayani, Masahiko Kurabayasi, Tatsuya Iso, Ratu Safitri, Ramdan Panigoro


BACKGROUND: Iron-overload cardiomyopathy (IOC) is a major comorbidity in patients with chronic repetitive blood transfusion due to myocardial iron uptake that facilitated by calcium channels. As cardiac compensatory mechanism to IOC, we hypothesized the cardiac calcium channels expression would be increased and involved in cardiomyopathy progressivity. This study was aimed to investigate the gene expression of calcium channels in the heart of the iron overload mice model.

METHODS: Mice were divided into three groups according to iron administration doses 0, 0.1, and 0.3 mg/day. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured for the representation of cardiovascular outcomes. The heart tissues were harvested. Further mRNA levels of L-type calcium channels (LTCCs) and T-type calcium channels (TTCCs) were examined using semi-quantitative PCR. The expressions of cardiac calcium channels and blood pressure among the three groups were compared.

RESULTS: The expressions of TTCCs in the two iron-injected groups were higher than the control group (p=0.018). The expressions of LTCCs were not different (p=0.413) among groups. SBP, DBP, and MAP of the iron-injected group were lower than the control group (p=0.025, p=0.011, and p=0.008, respectively).

CONCLUSION: Iron administration affects the expression of TTCCs but not the LTCCs, accompanied by decreasing of systolic and diastolic blood pressure.

KEYWORDS: cardiomyopathy, iron overload, L-type calcium channel, T-type calcium channel.

Full Text:



Borgna-Pignatti C, Gamberini MR. Complications of thalassemia major and their treatment. Expert Rev Hematol. 2011; 4: 353-66, CrossRef.

Kremastinos DT, Farmakis D, Aessopos A, Hahalis G, Hamodraka E, Tsiapras D, et al. Beta-thalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail. 2010; 3: 451-8. 3, CrossRef.

Moon SN, Han JW, Hwang HS, Kim MJ, Lee SJ, Lee JY, et al. Establishment of secondary iron overloaded mouse model: evaluation of cardiac function and analysis according to iron concentration. Pediatr Cardiol. 2011; 32: 947-52, CrossRef.

Eugene B. Cardiomyopathies. Circ Res. 2017; 121: 711-21, CrossRef.

Brieler J, Breeden MA, Tucker J. Cardiomyopathy: an overview. Am Fam Physician. 2017; 96: 640-6, article.

Cheng CF, Lian WS. Prooxidant mechanisms in iron overload cardiomyopathy. Biomed Res Int. 2013; 2013: 740573, CrossRef.

Kremastinos DT, Farmakis D. Iron overload cardiomyopathy in clinical practice. Circulation. 2011; 124: 2253-63, CrossRef.

Bornaun H, Dedeoglu R, Oztarhan K, Dedeoglu S, Erfidan E, Gundogdu M, et al. Detection of early right ventricular dysfunction in young patients with thalassemia major using tissue Doppler imaging. Iran J Pediatr. 2016; 26(3): e5808, CrossRef.

Aydinok Y, Porter JB, Piga A, Elalfy M, El-Beshlawy A, Kilinc Y, et al. Prevalence and distribution of iron overload in patients with transfusion-dependent anemias differs across geographic regions: results from the CORDELIA study. Eur J Haematol. 2015; 95: 244-53, CrossRef.

Gulati V, Harikrishnan P, Palaniswamy C, Aronow WS, Jain D, Frishman WH. Cardiac involvement in hemochromatosis. Cardiol Rev. 2014; 22: 56-68, CrossRef.

Shizukuda Y, Rosing DR. Iron overload and arrhythmias: Influence of confounding factors. J Arrhythmia. 2019; 35: 575-83, CrossRef.

Lopin KV, Gray IP, Obejero-Paz CA, Thévenod F, Jones SW. Fe2+ block and permeation of CaV3.1 (α1G) T-type calcium channels: candidate mechanism for non-transferrin-mediated Fe2+ influx. Mol Pharmacol. 2012; 82: 1194-204, CrossRef.

Kemp CD, Conte JV. The pathophysiology of heart failure. Cardiovasc Pathol. 2012; 21: 365-71, CrossRef.

Harvey PA, Leinwand LA. The cell biology of disease: cellular mechanisms of cardiomyopathy. J Cell Biol. 2011; 194: 355-65, CrossRef.

Chattipakorn N, Kumfu S, Fucharoen S, Chattipakorn S. Calcium channels and iron uptake into the heart. World J Cardiol. 2011; 3: 215-8, CrossRef.

Ono K, Iijima T. Cardiac T-type Ca(2+) channels in the heart. J Mol Cell Cardiol. 2010; 48: 65-70, CrossRef.

Kumfu S, Chattipakorn S, Srichairatanakool S, Settakorn J, Fucharoen S, Chattipakorn N. T-type calcium channel as a portal of iron uptake into cardiomyocytes of beta-thalassemic mice. Eur J Haematol. 2011; 86: 156-66, CrossRef.

Zhao X, Ho D, Gao S, Hong C, Vatner DE, Vatner SF. Arterial pressure monitoring in mice. Curr Protoc Mouse Biol. 2011; 1: 105-22, CrossRef.

Lawyer FC, Stoffel S, Saiki RK, Myambo K, Drummond R, Gelfand DH. Isolation, characterization, and expression in Escherichia coli of the DNA polymerase gene from Thermus aquaticus. J Biol Chem. 1989; 264: 6427-37, PMID.

Tabima DM, Hacker TA, Chesler NC. Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops. Am J Physiol Heart Circ Physiol. 2010; 299: H2069-75, CrossRef.

Gujja P, Rosing DR, Tripodi DJ, Shizukuda Y. Iron overload cardiomyopathy: better understanding of an increasing disorder. J Am Coll Cardiol. 2010; 56: 1001-12, CrossRef.

Das SK, Wang W, Zhabyeyev P, Basu R, McLean B, Fan D, et al. Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy. Sci Rep. 2015; 5(1): 18132, CrossRef.

Cribbs L. T-type calcium channel expression and function in the diseased heart. Channels (Austin). 2010; 4: 447-52, CrossRef.

Kumfu S, Chattipakorn S, Chinda K, Fucharoen S, Chattipakorn N. T-type calcium channel blockade improves survival and cardiovascular function in thalassemic mice. Eur J Haematol. 2012; 88: 535-48, CrossRef.

Komukai M, Tsutsumi T, Ebado M, Takeyama Y. Effect of an L- and T-type calcium channel blocker on 24-hour systolic blood pressure and heart rate in hypertensive patients. Korean Circ J. 2012; 42: 231-8, CrossRef.

Rose RA, Sellan M, Simpson JA, Izaddoustdar F, Cifelli C, Panama BK, et al. Iron overload decreases CaV1.3-dependent L-type Ca2+ currents leading to bradycardia, altered electrical conduction, and atrial fibrillation. Circ Arrhythm Electrophysiol. 2011; 4: 733-42, CrossRef.

Sequeira V, Nijenkamp LLAM, Regan JA, van der Velden J. The physiological role of cardiac cytoskeleton and its alterations in heart failure. Biochim Biophys Acta - Biomembr. 2014; 1838: 700-22, CrossRef.


Copyright (c) 2020 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute