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Short- and long-term effects of dronedarone on Cav3.1- and Cav3.2-T-type calcium channel current

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Published: 20 October 2026
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T-type calcium channels (TTCCs), including the Cav3.1 and Cav3.2 subtypes, play a critical role in regulating cardiac electrical activity. Their abnormal expression is closely associated with arrhythmias and cardiac dysfunction caused by myocardial infarction (MI). Dronedarone, a multi-target antiarrhythmic drug, is widely used to treat atrial fibrillation and atrial flutter but has shown adverse effects under pathological conditions such as MI. This study aims to investigate the direct effects and underlying mechanisms of dronedarone on TTCCs. Using neonatal rat cardiomyocytes, HEK293T cells transfected with Cav3.1 and Cav3.2, and MI rat model, we systematically analyzed the effects of dronedarone on TTCC activity. Dronedarone significantly inhibited Cav3.2 channel activity with an IC50 of 9.20 µM, while its effect on Cav3.1 was weaker (IC50 = 46.41 µM). Chronic treatment with dronedarone also slowed the activation and inactivation kinetics of TTCCs. In vivo experiments demonstrated that dronedarone exacerbated myocardial damage and fibrosis in the MI model. These findings suggest that dronedarone inhibits TTCC activity, particularly the Cav3.2 subtype, and alters its kinetic properties. This study reported the electrophysiological effects of dronedarone on T-type calcium channels, providing new insights into its electrophysiological properties and potential role in adverse cardiac events.

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1. Shah K, Seeley S, Schulz C, Fisher J, Gururaja Rao S. Calcium channels in the heart: disease states and drugs. Cells (Basel) 2022;11:943.
2. Fabritz L, Herzig S. Can T-type calcium channels make a change of heart after myocardial infarction? Fiction or fact, and for better or for worse? Cardiovasc Res 2011;91:373-5.
3. Le Quang K, Naud P, Qi X, Duval F, Shi Y, Gillis M, et al. Role of T-type calcium channel subunits in post-myocardial infarction remodelling probed with genetically engineered mice. Cardiovasc Res 2011;91:420-8.
4. Melgari D, Frosio A, Calamaio S, Marzi GA, Pappone C, Rivolta I. T-type calcium channels: a mixed blessing. Int J Mol Sci 2022;23:9894.
5. Kazemian P, Oudit G, Jugdutt BI. Atrial fibrillation and heart failure in the elderly. Heart Fail Rev 2012;17:597-613.
6. Wegener FT, Ehrlich JR, Hohnloser SH. Dronedarone: an emerging agent with rhythm- and rate-controlling effects. J Cardiovasc Electr 2006;17:S17-20.
7. Agelaki MG, Pantos C, Korantzopoulos P, Tsalikakis DG, Baltogiannis GG, Fotopoulos A, et al. Comparative antiarrhythmic efficacy of amiodarone and dronedarone during acute myocardial infarction in rats. Eur J Pharmacol 2007;564:150-7.
8. Aimond F, Beck L, Gautier P, Chérif OK, Davy JM, Lorente P, et al. Cellular and in vivo electrophysiological effects of dronedarone in normal and postmyocardial infarcted rats. J Pharmacol Exp Ther 2000;292:415-24.
9. No authors listed. Dronedarone in atrial fibrillation: too many questions about long-term adverse effects. Prescrire Int 2010;19:149-52.
10. Jiang X, Zhang Y, Zhang H, Zhang X, Yin X, Yuan F, et al. Acetate suppresses myocardial contraction via the short-chain fatty acid receptor GPR43. Front Physiol 2022;13:1111156.
11. Zheng M, Wang Y, Kang L, Shimaoka T, Marni F, Ono K. Intracellular Ca(2+)- and PKC-dependent upregulation of T-type Ca(2+) channels in LPC-stimulated cardiomyocytes. J Mol Cell Cardiol 2010;48:131-9.
12. Pantos C, Mourouzis I, Delbruyère M, Malliopoulou V, Tzeis S, Cokkinos DD, et al. Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal and postischemic performance of the isolated rat heart. Eur J Pharmacol 2002;444:191-6.
13. Gautier P, Guillemare E, Marion A, Bertrand J, Tourneur Y, Nisato D. Electrophysiologic characterization of dronedarone in guinea pig ventricular cells. J Cardiovasc Pharm 2003;41:191-202.
14. Marrouche NF, Dagher L, Wazni O, Akoum N, Mansour M, El Hajjar AH, et al. Effect of DrOnedarone on atrial fibrosis progression and atrial fibrillation recurrence postablation: Design of the EDORA randomized clinical trial. J Cardiovasc Electr 2021;32:3203-10.
15. Neef S, Maier LS. Novel aspects of excitation-contraction coupling in heart failure. Basic Res Cardiol 2013;108:360.
16. Kim H, Kim TH, Cha MJ, Lee JM, Park J, Park JK, et al. A Prospective Survey of Atrial Fibrillation Management for Real-world Guideline Adherence: COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) Registry. Korean Circ J 2017;47:877-87.
17. Boonhoh W, Kijtawornrat A, Sawangkoon S. Comparative effects of amiodarone and dronedarone treatments on cardiac function in a rabbit model. Vet World 2019;12:345-51.
18. Doggrell SA, Hancox JC. Dronedarone: an amiodarone analogue. Expert Opin Inv Drug 2004;13:415-26.
19. Linke J, Utpatel K, Wolke C, Evert M, Kühn J, Bukowska A, et al. Dronedarone does not affect infarct volume as assessed by magnetic resonance imaging in a porcine model of myocardial infarction. Mol Med Rep 2015;12:5169-78.
20. Sun W, Sarma JS, Singh BN. Electrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart : comparison with amiodarone. Circulation 1999;100:2276-81.
21. Bogdan R, Goegelein H, Ruetten H. Effect of dronedarone on Na+, Ca2+ and HCN channels. Naunyn-Schmiedeberg's Archives of Pharmacology 2011;383:347-56.
22. Powell KL, Cain SM, Ng C, Sirdesai S, David LS, Kyi M, et al. A Cav3.2 T-type calcium channel point mutation has splice-variant-specific effects on function and segregates with seizure expression in a polygenic rat model of absence epilepsy. J Neurosci 2009;29:371-80.
23. He M, Xu Z, Zhang Y, Hu C. Splice-variant-specific effects of primary aldosteronism point mutations on human Ca(V)3.2 calcium channels. Cell Calcium 2019;84:102104.
24. Wu H, Xie X, Sun M, Chen M, Tao X, Fang X, et al. Modification of mesenchymal stem cells by HMGB1 promotes the activity of Cav3.2 T-type calcium channel via PKA/β-catenin/γ-cystathionase pathway. Stem Cell Res Ther 2022;13:4.
25. Chang Y, Chen Y, Chen C. Identification of novel targeting sites of calcineurin and CaMKII in human Ca(V)3.2 T-type calcium channel. Biomedicines 2023;11:2891.
26. Yuan D, Cheng A, Kawahata I, Izumi H, Xu J, Fukunaga K. Single administration of the T-type calcium channel enhancer SAK3 reduces oxidative stress and improves cognition in olfactory bulbectomized mice. Int J Mol Sci 2021;22:741.

CRediT authorship contribution

Xuan Jiang, conceptualization, investigation, writing – original draft. Ligang Ding, conceptualization, investigation, writing – original draft. Mingqi Zheng, conceptualization, investigation, writing – original draft. Jianan Xu, data curation. Honghou He, data curation. Zelong Cao, formal analysis. Da Liu, formal analysis. Zhiyan Chen, formal analysis. All authors read and approved the final manuscript.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

How to Cite



1.
Jiang X, Xu J, He H, Cao Z, Liu D, Chen Z, et al. Short- and long-term effects of dronedarone on Cav3.1- and Cav3.2-T-type calcium channel current. Eur J Histochem [Internet]. 2026 Oct. 20 [cited 2026 Oct. 21];70(4). Available from: https://www.ejh.it/ejh/article/view/4534