Related Experiment Video
Updated: May 24, 2026
Ambulatory ECG Recording in Mice
Published on: May 27, 2010
T-type calcium channel blockade improves survival and cardiovascular function in thalassemic mice
Sirinart Kumfu1, Siriporn Chattipakorn, Kroekkiat Chinda
1Cardiac Electrophysiology Research and Training Center, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Insights
Iron overload in thalassemia damages the heart. Blocking T-type calcium channels (TTCC) and divalent metal transporter 1 (DMT1) reduced iron in the heart and liver, decreasing mortality in mice.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Molecular Biology
Background:
- Iron-overload cardiomyopathy is a significant complication in thalassemia patients.
- The exact mechanisms of iron uptake and storage in the heart remain unclear.
- Previous research implicated T-type calcium channels (TTCC) in iron uptake in thalassemic cardiomyocytes.
Purpose of the Study:
- To investigate the roles of TTCC, L-type calcium channels (LTCC), and divalent metal transporter 1 (DMT1) in iron entry into the heart in vivo.
- To evaluate the therapeutic potential of blocking these transporters in a mouse model of iron-overload cardiomyopathy.
Main Methods:
- Iron overload was induced in β-thalassemic mice using an iron-rich diet for 3 months.
- Mice were treated with blockers for LTCC, TTCC, DMT1, or an iron chelator (desferoxamine) for 1 month.
- Cardiac function, iron deposition, oxidative stress markers, and mortality were assessed.
Main Results:
- Treatment with LTCC, TTCC, DMT1 blockers, and desferoxamine reduced cardiac iron and improved left ventricular function.
- TTCC and DMT1 blockers, along with desferoxamine, also reduced liver iron accumulation and plasma oxidative stress.
- Only TTCC blockers provided benefits in both cardiac and liver iron reduction, alongside decreased mortality.
Conclusions:
- DMT1, LTCC, and TTCC are crucial for iron entry into the thalassemic heart during iron overload.
- TTCC blockers demonstrated comprehensive therapeutic benefits, including reduced iron burden in the heart and liver, attenuated oxidative stress, and decreased mortality.
- Targeting TTCC represents a promising therapeutic strategy for iron-overload cardiomyopathy in thalassemia.
Objectives:
Iron-overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. However, the precise mechanisms of iron entry and sequestration in the heart are still unclear. Our previous study showed that Fe(2+) uptake in thalassemic cardiomyocytes are mainly mediated by T-type calcium channels (TTCC). Nevertheless, the role of TTCC as well as other transporters such as divalent metal transporter1 (DMT1) and L-type calcium channels (LTCC) as possible portals for iron entry into the heart in in vivo thalassemic mice under an iron-overload condition has not been investigated.
Methods:
An iron-overload condition was induced in genetically altered β-thalassemic mice and adult wild-type mice by feeding them with an iron diet (0.2% ferrocene w/w) for 3 months. Then, blockers for LTCC (verapamil and nifedipine), TTCC (efonidipine), and DMT1 (ebselen) as well as iron chelator desferoxamine (DFO) were given for 1 month with continuous iron feeding.
Results:
Treatment with LTCC, TTCC, DMT1 blockers, and DFO reduced cardiac iron deposit, cardiac malondialdehyde (MDA), plasma non-transferrin-bound iron, and improved heart rate variability and left ventricular (LV) function in thalassemic mice with iron overload. Only TTCC and DMT1 blockers and DFO reduced liver iron accumulation, liver MDA, plasma MDA, and decreased mortality rate in iron-overloaded thalassemic mice.
Conclusions:
DMT1, LTCC, and TTCC played important roles for iron entry in the thalassemic heart under an iron-overloaded condition. Unlike LTCC blocker, TTCC blocker provided all benefits including attenuating iron deposit in both the heart and liver, reduced oxidative stress, and decreased mortality in iron-overloaded mice.
