2026-08-29T14:55:08Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/267572025-12-18T13:01:20Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Mondéjar-Parreño, Gema
author
Moreno-Manuel, Ana I
author
Ruiz-Robles, Juan Manuel
author
Jalife, José
funder
National Institutes of Health (Estados Unidos)
funder
Fundación La Caixa
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Marató TV3
funder
Ministerio de Universidades (España)
funder
Ministerio de Ciencia e Innovación (España)
funder
Fundación ProCNIC
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2025-06-17T09:52:44Z
2025-06-17T09:52:44Z
2025-01-10
Cell Discov. 2025 Jan 10;11(1):3.
Cell Discovery
39788950
https://hdl.handle.net/20.500.12105/26757
A well-balanced ion channel trafficking machinery is paramount for the normal electromechanical function of the heart. Ion channel variants and many drugs can alter the cardiac action potential and lead to arrhythmias by interfering with mechanisms like ion channel synthesis, trafficking, gating, permeation, and recycling. A case in point is the Long QT syndrome (LQTS), a highly arrhythmogenic disease characterized by an abnormally prolonged QT interval on ECG produced by variants and drugs that interfere with the action potential. Disruption of ion channel trafficking is one of the main sources of LQTS. We review some molecular pathways and mechanisms involved in cardiac ion channel trafficking. We highlight the importance of channelosomes and other macromolecular complexes in helping to maintain normal cardiac electrical function, and the defects that prolong the QT interval as a consequence of variants or the effect of drugs. We examine the concept of "interactome mapping" and illustrate by example the multiple protein-protein interactions an ion channel may undergo throughout its lifetime. We also comment on how mapping the interactomes of the different cardiac ion channels may help advance research into LQTS and other cardiac diseases. Finally, we discuss how using human induced pluripotent stem cell technology to model ion channel trafficking and its defects may help accelerate drug discovery toward preventing life-threatening arrhythmias. Advancements in understanding ion channel trafficking and channelosome complexities are needed to find novel therapeutic targets, predict drug interactions, and enhance the overall management and treatment of LQTS patients.
eng
Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.
research article
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URL
https://repisalud.isciii.es/bitstreams/2e07ad59-6a81-45ff-975f-edcfbcf70eda/download
File
MD5
376211be28bea06422e3e0aad13b50d3
2964622
application/pdf
Ion channel traffic jams_Cell Discov_2025.pdf