A New Strategy for Treating Atrial Fibrillation: Targeting the TRPC3 Channel

A research group led by Assistant Professor Megumi Aimoto and Professor Akira Takahara at the Faculty of Pharmaceutical Sciences, Toho University, revealed that pyrazole-3 (Pyr3), a selective inhibitor of the transient receptor potential canonical-3 (TRPC3) channel, a calcium-permeable channel in the heart, prevents the persistence of atrial fibrillation.
Atrial fibrillation is a tachyarrhythmia that occurs in the atria and is a major cause of stroke and heart failure. This study demonstrated that the TRPC3 channel is a promising new therapeutic target for atrial fibrillation. Drug therapy targeting TRPC3 channels is expected to provide a new approach for “overcoming” cardiovascular diseases associated with aging and lifestyle habits, including atrial fibrillation.
These findings were published in the Biological and Pharmaceutical Bulletin on October 15, 2025.

right: Prof. Akira Takahara,
left: First Author Dr. Megumi Aimoto

Key Points

TRPC3 channels are calcium-permeable channels involved in functional abnormalities in various organs such as blood vessels, kidneys, and nerves, and have attracted attention in the fields of lifestyle- and age-related diseases.
This study demonstrated that Pyr3, a selective TRPC3 channel inhibitor, significantly shortened the duration of atrial fibrillation in animal models with atrial remodeling.
Pyr3 suppresses the progression of intra-atrial conduction disturbances associated with atrial remodeling, thereby reducing the occurrence of sustained atrial fibrillation.
These results indicate that TRPC3 channels are novel therapeutic targets for preventing the onset and persistence of atrial fibrillation and suggest new strategies for overcoming cardiovascular diseases.

TRPC3 Inhibitor Effectively Suppresses Sustained Atrial Fibrillation in Rats
An aorto-venocaval shunt (AVS) produces chronic volume overload for ≥12 weeks, leading to the formation of arrhythmogenic substrates in the rat atria, and the TRPC3 inhibitor pyrazole-3 (Pyr3) effectively suppresses sustained atrial fibrillation.
ECG: electrocardiogram, RA: right atrial electrocardiogram, BP: blood pressure

Journal:
Biological and Pharmaceutical Bulletin (October 15, 2025) Vol. 48, No. 10, pp. 1547–1554

Article Title:
Anti-atrial Fibrillatory Effects of the TRPC3 Channel Inhibitor Pyrazole-3 in Rats with Atrial Enlargement Induced by Chronic Volume Overload

Authors:
Megumi Aimoto, Yoshinobu Nagasawa, Taichi Kusakabe, Keisuke Kato, Akira Takahara

DOI:
10.1248/bpb.b25-00415

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