Lgi3-4蛋白调节KV1.5通道小体，是心房颤动的潜在治疗靶点。
Socuéllamos, P.G., Macías, Á., Benito-Bueno, Á.d., Cruz, F.M., Redondo-Moya, M., Coronado, M.J., Ramil, E., Rosado, S., Rios-Rosado, E.C., Valencia-Avezuela, M., Andrés-Delgado, L., Blázquez, J.A., Forteza-Gil, A., Gutiérrez-Rodríguez, M., Jalife, J., & Valenzuela, C. (2026). Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.. Cardiovasc Res. https://doi.org/10.1093/cvr/cvag049
Socuéllamos PG, Macías Á, Benito-Bueno Ád, Cruz FM, Redondo-Moya M, Coronado MJ, et al. Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.. Cardiovasc Res. 2026; doi: 10.1093/cvr/cvag049
Socuéllamos PG, Macías Á, Benito-Bueno Ád, et al. Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.[J]. Cardiovasc Res. 2026. DOI: 10.1093/cvr/cvag049.
@article{socullamos2026,
author = {Paula G Socuéllamos and Álvaro Macías and Ángela de Benito-Bueno and Francisco M Cruz and María Redondo-Moya and María José Coronado and Elvira Ramil and Silvia Rosado and Elsa Carolina Rios-Rosado and María Valencia-Avezuela and Laura Andrés-Delgado and José Antonio Blázquez and Alberto Forteza-Gil and Marta Gutiérrez-Rodríguez and José Jalife and Carmen Valenzuela},
title = {Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation.},
journal = {Cardiovasc Res},
year = {2026},
doi = {10.1093/cvr/cvag049},
note = {PMID: 41854369},
}
TY - JOUR AU - Paula G Socuéllamos AU - Álvaro Macías AU - Ángela de Benito-Bueno AU - Francisco M Cruz AU - María Redondo-Moya AU - María José Coronado AU - Elvira Ramil AU - Silvia Rosado AU - Elsa Carolina Rios-Rosado AU - María Valencia-Avezuela AU - Laura Andrés-Delgado AU - José Antonio Blázquez AU - Alberto Forteza-Gil AU - Marta Gutiérrez-Rodríguez AU - José Jalife AU - Carmen Valenzuela TI - Lgi3-4 proteins modulate the KV1.5 channelosome and are potential therapeutic targets for atrial fibrillation. T2 - Cardiovasc Res PY - 2026 DO - 10.1093/cvr/cvag049 AN - PMID:41854369 ER -
We investigated the role of Lgi3-4 proteins in cardiac electrophysiology, with a specific focus on IKur, and their potential contribution to the pathophysiology of atrial fibrillation (AF). In human atrial tissue and heterologous cells, Lgi3 and Lgi4 interacted with KV1.5 channels. In a mouse model of AAV9-mediated cardiac-specific Lgi4 expression, sinoatrial and atrioventricular conduction were impaired, resulting in a prolonged QRS interval. Action potential repolarisation was delayed in atrial and ventricular cardiomyocytes from Lgi4 mice. In HEK293 cells, Lgi3-4 impaired KV1.5/KVβ association, partially reversing the KVβ-induced inactivation and reducing IKur amplitude. These results correlated with the reduced KV1.5 membrane expression and IKur density observed in Lgi4 cardiomyocytes and HEK293 cells. Notably, Lgi4 protein expression was lower in atrial tissue from patients with AF than in sinus rhythm patients. The reduced Lgi4 protein levels in AF were also associated with an altered colocalisation with KV1.5 channels, suggesting potential disruption in their functional interactions. We conclude that Lgi3-4 proteins are new components of the cardiac KV1.5 channelosome. They modulate IKur by interfering with the KV1.5-KVβ interaction. Significantly, Lgi4 is dysregulated differently in paroxysmal vs. permanent AF. The results identify Lgi3-4 proteins as novel regulators of the KV1.5 channelosome, opening new pathways for investigating the role of IKur dysfunction in the mechanism of atrial fibrillation.