دورية أكاديمية
Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation.
| العنوان: | Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation. |
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| المؤلفون: | Mesirca, Pietro, Alig, Jacqueline, Fernandez, Anne, Seniuk, Anika, Engeland, Birgit, Singh, Jasmin, Miquerol, Lucile, Ehmke, Heimo, Eschenhagen, Thomas, Nargeot, Joel, Wickman, Kevin, Isbrandt, Dirk, Torrente, Angelo G, Mangoni, Matteo E, Müller, Jana Christina, Marger, Laurine, Rollin, Anne, Marquilly, Claire, Vincent, Anne, Dubel, Stefan, Bidaud, Isabelle |
| المصدر: | Nature Communications 5(1), 4664 (2014). doi:10.1038/ncomms5664 |
| بيانات النشر: | Nature Publishing Group UK |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/500, Animals, Arrhythmias, Cardiac: drug therapy, Cardiac: genetics, Cardiac: physiopathology, Benzazepines: pharmacology, Calcium Signaling: genetics, Disease Models, Animal, Female, G Protein-Coupled Inwardly-Rectifying Potassium Channels: genetics, G Protein-Coupled Inwardly-Rectifying Potassium Channels: metabolism, Heart Rate: drug effects, Humans, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: genetics, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: metabolism, Ivabradine, Male, Mice, Inbred C57BL, Transgenic, Muscle Proteins: genetics, Muscle Proteins: metabolism, Myocytes, Cardiac: metabolism, Cardiac: pathology, Oocytes: physiology, Patch-Clamp Techniques, Potassium Channels: genetics |
| جغرافية الموضوع: | DE |
| الوصف: | The mechanisms underlying cardiac automaticity are still incompletely understood and controversial. Here we report the complete conditional and time-controlled silencing of the 'funny' current (If) by expression of a dominant-negative, non-conductive HCN4-channel subunit (hHCN4-AYA). Heart-specific If silencing caused altered [Ca(2+)]i release and Ca(2+) handling in the sinoatrial node, impaired pacemaker activity and symptoms reminiscent of severe human disease of pacemaking. The effects of If silencing critically depended on the activity of the autonomic nervous system. We were able to rescue the failure of impulse generation and conduction by additional genetic deletion of cardiac muscarinic G-protein-activated (GIRK4) channels in If-deficient mice without impairing heartbeat regulation. Our study establishes the role of f-channels in cardiac automaticity and indicates that arrhythmia related to HCN loss-of-function may be managed by pharmacological or genetic inhibition of GIRK4 channels, thus offering a new therapeutic strategy for the treatment of heart rhythm diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/issn/2041-1723; info:eu-repo/semantics/altIdentifier/pmid/pmid:25144323; https://pub.dzne.de/record/137523Test; https://pub.dzne.de/search?p=id:%22DZNE-2020-03845%22Test |
| الإتاحة: | https://doi.org/10.1038/ncomms5664Test https://pub.dzne.de/record/137523Test https://pub.dzne.de/search?p=id:%22DZNE-2020-03845%22Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.7D43BAC8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |