What is the clinical evidence from this study?

Study design: Other. Population: Antidepressant-induced Brugada syndrome. Intervention: Amitriptyline vs. Control cells (no amitriptyline). Primary outcome: Peak INa density at -35 mV (56.6% decrease, p=<0.001).

September 5, 2018Frontiers in PhysiologyOpen Access

Key Role of the Membrane Trafficking of Nav1.5 Channel Protein in Antidepressant-Induced Brugada Syndrome

Q: What are the key findings of this study?

Long-term treatment with amitriptyline reduced peak Nav1.5 sodium current density by 56.6% in neonatal rat ventricular myocytes, driven by disrupted Nav1.5 trafficking to the cell membrane.

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Key result

Long-term amitriptyline reduces peak Nav1.5 current density ~57% in rat myocytes via disrupted membrane trafficking.

56.6% decrease
P<0.001

Population

Neonatal rat ventricular myocytes

Comparison

Amitriptyline (acute and chronic exposure) vs Control / acute vs chronic exposure

Design

Preclinical

Authors

XCXi ChenHenan University Huaihe Hospital and Huaihe Clinical Institute CZChao ZhuBengbu Medical College HZHao ZhouFujian University of Traditional Chinese Medicine

Discussion

Member takes

Implication

Supports caution with amitriptyline in BrS-susceptible patients; leaves open Nav1.5 mechanisms in human cardiomyocytes.

Structured PICO

Population

In vitro study using neonatal rat ventricular myocytes to investigate the electrophysiological and molecular effects of acute and long-term amitriptyline exposure on Nav1.5 channels.

Intervention

Amitriptyline (acute and chronic exposure)

Comparator

Control / acute vs chronic exposure

Outcome

Electrophysiological properties, expression and distribution of Nav1.5, and interactions with ankyrin-G and dystrophinsurrogate

Main Result

Effect estimate: 56.6% decrease

Absolute Event Rate: -125.2% vs -288.8%

p-value: p=<0.001

Chronic amitriptyline exposure may contribute to Brugada syndrome by disrupting Nav1.5 channel trafficking and its interaction with ankyrin-G and dystrophin.

Limitations

Used neonatal rat ventricular myocytes instead of adult rat myocytes, preventing observation of specific locations on intercalated disks and lateral membranes.
Impacts of other antidepressants on Nav1.5 protein expression and distribution were not fully studied.
Only two Nav1.5-interacting proteins (ankyrin-G and dystrophin) were investigated, while others like Kir2.x may also play important roles.

Cite This Study

Chen et al. (2018) studied Antidepressant-induced Brugada syndrome. Amitriptyline vs. Control cells (no amitriptyline) was evaluated on Peak INa density at -35 mV (56.6% decrease, p=<0.001). Long-term treatment with amitriptyline reduced peak Nav1.5 sodium current density by 56.6% in neonatal rat ventricular myocytes, driven by disrupted Nav1.5 trafficking to the cell membrane.

synapsesocial.com/papers/6aa4e208881927c3e1811d3d https://doi.org/10.3389/fphys.2018.01230

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Key Role of the Membrane Trafficking of Nav1.5 Channel Protein in Antidepressant-Induced Brugada Syndrome

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Key Role of the Membrane Trafficking of Nav1.5 Channel Protein in Antidepressant-Induced Brugada Syndrome

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider