Fluorescent membrane potential assay for drug screening on Kv10.1 channel: identification of BL-1249 as a channel activator

Frontiers in Pharmacology

Pharmacology

Enikar Patlán¹  Mirsha Aseret Gómez-Herrera¹  Arturo Hernández-Cruz¹  Enoch Luis²  Armando Estrada-Garrido³ 

[1] Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico;Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico;Cátedras CONAHCYT—Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico;Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico;Universidad Tecnológica de México (UNITEC)—Campus Ecatepec, Estado de México, Mexico;

关键词: membrane potential;    Kv10.1;    oncochannel;    Kv opener;    cell-based fluorescent assay;   

DOI  :  10.3389/fphar.2023.1238503

 received in 2023-06-11, accepted in 2023-07-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Resting membrane potential is a bioelectric property of all cells. Multiple players govern this property, the ion channels being the most important. Ion channel dysfunction can affect cells’ resting membrane potential and could be associated with numerous diseases. Therefore, the drug discovery focus on ion channels has increased yearly. In addition to patch-clamp, cell-based fluorescent assays have shown a rapid and reliable method for searching new ion channel modulators. Here, we used a cell-based membrane potential assay to search for new blockers of the Kv10.1, a potassium channel strongly associated with cancer progression and a promising target in anticancer therapy. We found that fluoxetine and miconazole can inhibit the Kv10.1 channel in the micromolar range. In contrast, BL-1249 potentiates Kv10.1 currents in a dose-dependent manner, becoming the first molecule described as an activator of the channel. These results demonstrate that cell-based membrane potential assay can accelerate the discovery of new Kv10.1 modulators.

【 授权许可】

Unknown   
Copyright © 2023 Gómez-Herrera, Patlán, Estrada-Garrido, Hernández-Cruz and Luis.