Why the study?
Whether tetrodotoxin-sensitive sodium channel isoforms directly contribute to pathological late sodium current and arrhythmogenesis was unresolved due to a lack of isoform-selective pharmacological tools.
Does selective activation of TTX-S sodium channels by AaH-II drive arrhythmogenic late Na+ current in the heart?
Population
Human iPS-derived cardiomyocytes, adult ventricular cardiomyocytes, isolated hearts, and in vivo models
Comparison
AaH-II vs reference inducer ATX-II or nanomolar tetrodotoxin
Design
Preclinical experimental study
Key result
AaH-II selectively activates tetrodotoxin-sensitive sodium channels to generate arrhythmogenic late Na+ current, causing conduction abnormalities and QT prolongation independently of Nav1.5.
Authors
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Challenges Nav1.5-centric arrhythmia models; hypothesis-generating for TTX-S targeting but requires human validation before any therapeutic consideration.
Does selective activation of TTX-S sodium channels by AaH-II drive arrhythmogenic late Na+ current in the heart?
Selective activation of TTX-S sodium channels is sufficient to generate arrhythmogenic late Na+ current independently of Nav1.5, suggesting a novel target for antiarrhythmic therapy.
Millet et al. (2026) studied Cardiac arrhythmias. AaH-II vs. ATX-II was evaluated on Late sodium current (INaL) activation and arrhythmogenesis. AaH-II selectively activates tetrodotoxin-sensitive sodium channels to generate arrhythmogenic late Na+ current, causing conduction abnormalities and QT prolongation independently of Nav1.5.