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

Q: What are the key findings of this study?

Dronedarone significantly inhibited T-type calcium channel activity, specifically reducing Cav3.2 channel current density from -5.64 pA/pF to -1.59 pA/pF with an IC50 of 9.20 µM.

Q: What is the clinical evidence from this study?

Population: Myocardial infarction. Intervention: Dronedarone vs. Vehicle or before drug application. Primary outcome: Cav3.2 channel current density at -40 mV (peak) in transfected HEK293T cells exposed to 10 µM dronedarone (p=<0.01).

Q: What does this research mean for the field?

Dronedarone inhibits cardiac T-type calcium channel activity, preferentially suppressing Cav3.2 channel current density with an IC50 of 9.20 µM, while altering channel gating kinetics and exacerbating post-infarction myocardial damage. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To investigate the direct acute and chronic effects and electrophysiological mechanisms of dronedarone on T-type calcium channel subtypes Cav3.1 and Cav3.2.

Xuan Jiang; Jianan Xu; Honghou He; Zelong Cao; Da Liu; Zhiyan Chen; Ligang Ding; Mingqi Zheng

doi:10.4081/ejh.2026.4534

October 20, 2026European Journal of HistochemistryOpen Access

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

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Key result

Dronedarone reduces Cav3.2 T-type calcium channel current density by ~72%.

P<0.01

Why the study?

Dronedarone is widely used to treat atrial fibrillation and flutter but has shown adverse effects under pathological conditions such as myocardial infarction, with unclear direct effects on T-type calcium channels.

Does dronedarone inhibit T-type calcium channel activity and what are its effects in a myocardial infarction model?

Key Points

To investigate the direct acute and chronic effects and electrophysiological mechanisms of dronedarone on T-type calcium channel subtypes Cav3.1 and Cav3.2.
Assessed total T-type calcium channel currents in neonatal rat cardiomyocytes and heterologously expressed human Cav3.1 (CACNA1G) and Cav3.2 (CACNA1H) in HEK293T cells using patch-clamp electrophysiology.
Evaluated chronic channel kinetics after 48-hour dronedarone exposure in Cav3.2-transfected HEK293T cells.
Administered dronedarone (30 mg/kg/d by gavage for 14 days) or vehicle to rats 8 weeks after myocardial infarction to assess cardiac function, electrocardiograms, and myocardial histology.
Dronedarone inhibited Cav3.2 channel activity with an IC50 of 9.20 µM and significantly reduced current density at -40 mV from -5.64±0.85 pA/pF to -1.59±0.40 pA/pF (p<0.01), whereas its inhibition of Cav3.1 was weaker with an IC50 of 46.41 µM.
In neonatal cardiomyocytes, dronedarone blocked T-type calcium channels with an IC50 of 3.682 µM and reduced current density at -30 mV from -4.18±0.58 pA/pF to -1.71±0.36 pA/pF (p<0.01).
In vivo, dronedarone failed to rescue ejection fraction or prolonged QRS and QT intervals, while decreasing Cav3.2 expression from 23.00±1.52 to 17.00±1.15 (p<0.05) and worsening myocardial damage and fibrosis.

Structured PICO

Does dronedarone inhibit T-type calcium channel activity and what are its effects in a myocardial infarction model?

P

Population

Preclinical study utilizing adult male Wistar rats with induced myocardial infarction, neonatal rat cardiomyocytes, and HEK293T cells to assess the electrophysiological effects of dronedarone.

I

Intervention

Dronedarone (30 mg/kg/day via gavage for 14 days in rats; in vitro applied acutely at concentrations from 0.1 to 40 µM, or chronically at 1 µM for 48 hours).

C

Comparator

Vehicle control for in vivo rat models; untreated cells or baseline pre-application measurements for in vitro models.

O

Outcome

Inhibition of T-type calcium channel current activity and kinetics (Cav3.1 and Cav3.2); cardiac function (ejection fraction, fractional shortening) and electrocardiographic parameters (QRS and QT intervals) in MI rats.surrogate

Main Result

Absolute Event Rate: -1.59% vs -5.64%

p-value: p=<0.01

Dronedarone inhibits T-type calcium channels, particularly the Cav3.2 subtype, providing mechanistic insight into why it may exacerbate cardiac damage and prolong QT intervals in post-myocardial infarction settings.

Limitations

Using (-100) mV and (-50) mV holding potentials and subtracting currents may not fully isolate L- and T- type calcium channel in neonatal cardiomyocytes.
The research is primarily based on neonatal rat cardiomyocytes and transfected HEK293T cells, without further validation in adult cardiomyocytes.
The specific molecular mechanisms underlying the inhibition of T-type calcium channels by dronedarone (e.g., direct binding vs indirect regulation) were not thoroughly investigated.
Research is primarily based on neonatal rat cardiomyocytes and transfected HEK293T cells, without further validation in adult cardiomyocytes.

Implication

May worsen post-MI injury and fibrosis in rats; hypothesis-generating for T-type channel effects in human cardiac pathology.

Abstract

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.

Discussion

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Cite This Study

Jiang et al. (2026) studied Myocardial infarction. Dronedarone vs. Vehicle or before drug application was evaluated on Cav3.2 channel current density at -40 mV (peak) in transfected HEK293T cells exposed to 10 µM dronedarone (p=<0.01). Dronedarone significantly inhibited T-type calcium channel activity, specifically reducing Cav3.2 channel current density from -5.64 pA/pF to -1.59 pA/pF with an IC50 of 9.20 µM.

synapsesocial.com/papers/6ad8a1e74fe90d57c13299d3 https://doi.org/10.4081/ejh.2026.4534

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

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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