Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome
Abstract 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, g...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-024-00738-0 |
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| author | Gema Mondéjar-Parreño Ana I. Moreno-Manuel Juan Manuel Ruiz-Robles José Jalife |
| author_facet | Gema Mondéjar-Parreño Ana I. Moreno-Manuel Juan Manuel Ruiz-Robles José Jalife |
| author_sort | Gema Mondéjar-Parreño |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-cabffa1e60b347fab9a23e952b888d41 |
| institution | Kabale University |
| issn | 2056-5968 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj-art-cabffa1e60b347fab9a23e952b888d412025-01-12T12:07:58ZengNature Publishing GroupCell Discovery2056-59682025-01-0111112610.1038/s41421-024-00738-0Ion channel traffic jams: the significance of trafficking deficiency in long QT syndromeGema Mondéjar-Parreño0Ana I. Moreno-Manuel1Juan Manuel Ruiz-Robles2José Jalife3Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro Nacional de Investigaciones Cardiovasculares (CNIC)Abstract 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.https://doi.org/10.1038/s41421-024-00738-0 |
| spellingShingle | Gema Mondéjar-Parreño Ana I. Moreno-Manuel Juan Manuel Ruiz-Robles José Jalife Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome Cell Discovery |
| title | Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome |
| title_full | Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome |
| title_fullStr | Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome |
| title_full_unstemmed | Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome |
| title_short | Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome |
| title_sort | ion channel traffic jams the significance of trafficking deficiency in long qt syndrome |
| url | https://doi.org/10.1038/s41421-024-00738-0 |
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